Symptoms and General Pathology

All Conditions

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Immune System Diseases

Rare Diseases

Inflammation

Osteoarthritis

Arthritis

Necrosis

Psoriasis

Autoimmune Diseases

Arthritis, Rheumatoid

Pain

Joint Diseases

Rheumatic Diseases

Collagen Diseases

Connective Tissue Diseases

Chronic Graft Versus Host Disease

Micronutrients

All Drugs and Chemicals

Bone Density Conservation Agents

Other Dietary Supplements

Vitamins

Vitamin D

Cholecalciferol

Ergocalciferols

Trace Elements

Hormones

Calcium

Calcium, Dietary

Omega 3 Fatty Acid

Vitamin D3

Calciferol

Ergocalciferol

Vitamin D2

Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]).

Subjects will receive vitamin D3 (cholecalciferol) 2000 IU a day.

Fish Oil

placebo pill

Karen H Costenbader, MD, MPH

The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is a randomized clinical trial in 25,871 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. This ancillary study is being conducted among VITAL participants and will examine whether vitamin D or fish oil have effects upon A) autoimmune disease incidence, B) biomarkers of systemic inflammation, and C) chronic knee pain. Blood samples at baseline and in follow-up will be collected in a randomly selected subcohort of 1500 individuals and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein, interleukin-6, and tumor necrosis factor-receptor 2. Approximately 1300 individuals with chronic, frequent knee pain will be followed with annual questionnaires to evaluate the effects of the supplements on chronic knee pain.

Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Knee Pain

In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the IL-6 serum biomarker of systemic inflammation.

In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the CRP serum biomarker of systemic inflammation.

In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the TNFR2 serum biomarker of systemic inflammation.

All participants were followed for the development of new autoimmune diseases, including, but not limited to, rheumatoid arthritis, psoriasis, autoimmune thyroid disease, inflammatory bowel disease and polymyalgia rheumatica. The primary endpoint was all incident autoimmune disease confirmed by extensive medical record review. Participants self-reported all incident autoimmune diseases from baseline through follow-up. We used Cox proportional hazards models to test the effects of vitamin D and n-3 fatty acids upon autoimmune disease incidence.

We compared the separate main effects of vitamin D or n-3 fatty acid supplement assignment on AD incidence using Cox regression models. To account for randomization stratification and study design, we additionally adjusted for age, sex, self-reported race, and randomization to the other supplement. Person-time was counted until diagnosis of a new confirmed AD, death, or the end of the trial. We also test interactions between the two supplements

Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Pain was the primary outcome on a scale of 0-100 with 100= worst pain.

Subsample of VITAL participants with chronic, frequent knee pain at trial baseline were followed with annual WOMAC questionnaires to test for change in severity of chronic knee pain in those taking Omega-3 fish oil (n-3 FA) supplements compared to those taking placebo and for those taking Vitamin D supplements compared to those taking placebo. We tested whether n-3 FA supplements and Vitamin D are associated with reduced levels of WOMAC knee pain at the end of the trial (comparing knee pain outcomes in those receiving supplements to placebo). We will also test whether there were multiplicative interactions between the two supplements for the outcome of knee pain severity by WOMAC-Pain index

Development of new autoimmune disease through observational follow-up after trial termination.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Brigham and Women's Hospital

Associate Physician

Vit D Monitored safety cond'ns: hypercalcemia, kidney stones, parathyroid disease, kidney failure or dialysis; Other symptoms, side effects: GI bleeding, easy bruising; stomach upset or pain; nausea; constipation, diarrhea, skin rash

Omega-3 FA Monitored safety cond'ns: GI bleeding; blood in urine; easy bruising; freq nosebleeds; kidney failure or dialysis; Other symptoms, side effects: stomach upset or pain; nausea; constipation; diarrhea; skin rash; bad taste in mouth; increased burping

Vitamin D3, one 2000 IU capsule/day

Omacor, one 1-g capsule/day. Each capsule of Omacor contains 840 mg of marine omega-3 fatty acids (465 mg of EPA + 375 mg of DHA).

Active Vitamin D/ Active Omega-3 Fatty Acids

Vitamin D3, one 2000 IU capsule/day

Omega-3 fatty acids placebo, one capsule/day

Active Vitamin D/ Active Omega-3 Placebo

Omacor, one 1-g capsule/day. Each capsule of Omacor contains 840 mg of marine omega-3 fatty acids (465 mg of EPA + 375 mg of DHA).

Vitamin D placebo, one capsule/day

Active Omega-3 Fatty Acids, Placebo Vitamin D

Omega-3 fatty acids placebo, one capsule/day

Vitamin D placebo, one capsule/day

Omega-3 Fatty Acids Placebo/ Placebo Vitamin D

ACTIVE Vitamin D = Vitamin D3, one 2000 IU capsule/day; ACTIVE Omega-3 Fatty Acids = Omacor, one 1-gram capsule/day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]).

ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids

ACTIVE Vitamin D = Vitamin D3, one 2000 IU capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day

ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids

PLACEBO Vitamin D, one capsule/day; ACTIVE Omega-3 Fatty Acids = Omacor, one 1-gram capsule/day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]).

PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids

PLACEBO Vitamin D, one capsule/day; PLACEBO Omega-3 Fatty Acids, one capsule/day

PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids

Total

Age, Categorical

Age, Continuous

Female

Male

Sex/Gender, Customized

Non-Hispanic white

African American

Hispanic (not African American)

Asian/Pacific Islander

Native American/ Alaskan Native

Other/ unknown

Race/Ethnicity measured using different categories in systemic inflammation versus knee pain subcohorts.

Race/Ethnicity, Customized

United States

Region of Enrollment

In this 2x2 factorial design trial, the primary analyses were: all active vitamin D vs. all placebo vitamin D and all active omega-3 fatty acids vs. all placebo omega-3 fatty acids.

Karen Costenbader

Geometric means of biomarker concentrations with 95% CIs were calculated for baseline and 1 year biomarkers (IL-6, TNFR2 and CRP) by treatment group (active vs. placebo vitamin D). Linear repeated measures models calculated the % change in means for each biomarker from baseline to year one and the overall effects of randomized treatments with 95% CIs.

Test for interaction between effect of vitamin D and effect of omega-3 fatty acids on IL-6 change from baseline to 1 year

Baseline ln (IL-6) pg/ml, geometric mean (95% Cl)

Year 1 ln (IL-6) pg/mL, geometric mean (95% CI)

Active Vitamin D

Placebo Vitamin D

Omacor, one 1-g capsule/day. Each capsule of Omacor contains 840 mg of marine omega-3 fatty acids (465 mg of EPA + 375 mg of DHA).

Active n-3 FA

Omega-3 fatty acids placebo, one capsule/day

Placebo n-3 FA

Subsample of the VITAL trial participants at baseline and one year.

Serum Levels of Biomarkers of Systemic Inflammation: Interleukin-6 (IL-6)

Test for multiplicative interaction between effect of vitamin D and effect of omega-3. based on linear models of ln biomarker from baseline to year 1.

Baseline ln (hsCRP) mg/L, geometric mean (95% Cl)

Year 1 ln (hsCRP) mg/L, geometric mean (95% CI)

Serum Levels of Biomarkers of Systemic Inflammation: C-reactive Protein (CRP)

Baseline ln (TNFR2) pg/ml, geometric mean (95% Cl)

Year 1 ln (TNFR2) pg/mL, geometric mean (95% CI)

Serum Levels of Biomarkers of Systemic Inflammation: Tumor Necrosis Factor-receptor 2 (TNFR2)

Test for multiplicative interaction between the effects of randomized treatment groups, vitamin D and n-3 fa on incidence of autoimmune disease.

All participants in VITAL followed for the development of new autoimmune diseases, including, but not limited to, rheumatoid arthritis, psoriasis, autoimmune thyroid disease, inflammatory bowel disease and polymyalgia rheumatica. Categorized by vitamin D (active/placebo) and n-3 (active/placebo)

Incident Autoimmune Diseases

Intention to treat analysis using a repeated measures model with unstructured variance to assess the effect of treatment arm on WOMAC Pain adjusting for age, sex, and the other treatment arm. The linear time by treatment interaction term assessed change in WOMAC Pain over time between participants randomized to treatment versus placebo.

We assessed for effect modification between vitamin D and N-3 FA and tested for other pre-specified interactions. We again used a repeated measures model with censoring for TKR. We adjusted for age, sex and N-3 FA treatment arm (in analyses in which N-3 FA treatment arm was not investigated as a potential modifier).

Active n3fa vs placebo n3fa among those on placebo vitamin D.

Vitamin D vs. vitamin D placebo among those on placebo omega-3 fatty acids- stratified analyses.

Omega-3 fatty acids vs. omega-3 fatty acids placebo among those on active vitamin D.

Omega-3 fatty acids vs. omega-3 fatty acids placebo among those on placebo vitamin D.

Baseline mean WOMAC Pain

Follow Up mean WOMAC pain

Omacor, one 1-g capsule/day. Each capsule of Omacor contains 840 mg of marine omega-3 fatty acids (465 mg of EPA + 375 mg of DHA) + Vitamin D3, one 2000 IU capsule/day or Vitamin D placebo, one capsule/day

Omega-3 fatty acids placebo, one capsule/day + Vitamin D3, one 2000 IU capsule/day or Vitamin D placebo, one capsule/day

Vitamin D3, one 2000 IU capsule/day + Omega 3 Omacor fatty acid, 1-g capsule/day or Omega-3 fatty acid placebo

Placebo vitamin D3, one 2000 IU capsule/day + Omega 3 Omacor fatty acid, 1-g capsule/day or Omega-3 fatty acid placebo

Subsample of the VITAL trial who reported chronic frequent knee pain prior to randomization.

Severity of Knee Pain in Subsample With Chronic, Frequent Knee Pain at Baseline- With n-3 FA & Vitamin D

Incident Autoimmune Disease

Overall Study

Neoplasms

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

3,3'-diindolylmethane

75 mg of 3,3´-diindolylmethane (DIM) once a day for 30 days

Two pills of BioResponse DIM® 150 are equal to 75 mg of DIM pure

DIM pills

Placebo pills, proportionate by the same provider, vials and pills were the same size, shape and material containing the DIM pills

Placebo Pill

Breast cancer is a public health problem in Mexico and its incidence rises when the woman is still premenopausal. Estrogen metabolism has been linked to breast cancer. Several studies reported that high concentrations of 2 hydroxyestrone (2OHE1) in urine have a protective effect for this neoplasia, whereas high concentrations of 16 alpha-hydroxyestrone (16αOHE1) in urine have the opposite effect, further has been reported that women with a ratio of estrogen metabolites 2OHE1:16αOHE1 in urine (REMU) less than 0.9, have ten times the risk of developing Breast Cancer than those women with an RMEU equal or more than 0.9. Other studies have showed that the active compounds of cruciferous vegetables, indole-3-carbinol (I3C) and its dimer, 3'3'diindolylmethane (DIM) induce benign pathway of metabolism of estrogens producing 2OHE1. Several studies, evaluate the pharmacokinetics and effect of I3C supplementation, finding that 300 to 600 mg of this compound are well tolerated and able to promote formation of 2OHE1 in women when supplemented for one month. In the case of DIM, only a pilot study has explored its effect in postmenopausal women with personal history of breast cancer in early stages, reporting an increase in the concentrations of 2OHE1. The purpose of this study was to evaluate the effectiveness of supplementation with DIM to increase urinary RMEU in premenopausal women at risk of Breast Cancer (RMEU less than 0.9). A clinical, randomized, double-blind study was performed with women attending on the urogynecology service of Institute National of Perinatology. Subjects were premenopausal women over 34 years who were healthy. The inclusion criteria's was had a RMEU less than 0.9 and were excluded for any medical condition, medication, or dietary or lifestyle habit that might interfere with estrogen metabolism. Patients were randomly assigned to one of two groups: one received orally at a daily dose of 75 mg of DIM for a period of 30 days and other group received orally at a daily placebo for a period of 30 days. All urine samples were collected from the women before DIM or placebo ingestion, after 30 days of DIM or placebo ingestion and finally after another 30 days once suspended supplementation. Analysis of the 2OHE1 and 16αOHE1 were determined using a commercially kit ESTRAMET™. The change in metabolites median concentrations and RMEU was assessed through the Wilcoxon test and these differences between groups through U Mann-Whitney test.

The purpose of this study was to evaluate the effectiveness of supplementation with 3,3´-Diindolylmethane (DIM) to increase the urinary ratio of estrogen metabolites 2OHE1:16alphaOHE1 (RMEU) in women at risk of breast cancer to contribute to generate a tool of early prevention of this disease.

Activities for detect women with REMU less than 0.9:

Check every day in the Institute National of Perinatology urogynecology service, clinical records of the women who attending consultations in order to verify the inclusion and exclusion criteria.

Interviewing these women to corroborate the inclusion and exclusion criteria. Quantify the concentrations of metabolites of estrogens in the urine for detect the presence of REMU less than 0.9.

Provide result and invite women who present REMU less than 0.9 to participate in the project of supplementation with DIM.

When women had a REMU equal or greater than 0.9, provide result and dietary guidance focused on maintaining BMI in normal range (19.0-24.9) or decrease (BMI more than or equal to 25) weight and the increase in the consumption of fruits and vegetables.

Activities for women inclusion in the study of DIM supplementation:

Once explained the study to the patients, women who met the criteria for inclusion were cited to provide an informed consent letter mentioning them that they had the freedom to clarify any doubt that might arise.

Once the woman read out the letter, understood it and agreed to participate, the signing of this was requested.

On the same date that each woman has signed the letter, another appointment was scheduled between day 12 and 15 of the menstrual cycle for the following assessments:

Personal data: Name, date of birth, address, phone, marital status and occupation.

Socioeconomic: With the criteria of the Mexican Association of Agencies of Market and Opinion based 2005

Complete clinical history that included:

Family history of chronic diseases included breast cancer, personal history of diseases and use medication, personal risk factors of breast cancer, type, frequency and duration of physical activity.

Nutrition: Whereas both anthropometric indicators (weight, height and perimeter wrist, waist and hip), body composition (% of body fat and lean mass by the method of displacement of air) and diet (24-hour recall, frequency of consumption of cruciferous vegetables in the last year and use of supplements). The measurements of anthropometric indicators were made using the LOHMAN technique. The information was processed with the NUTRIKCAL system that is standardized for foods commonly consumed in Mexico.

First morning urine. First morning urine with a difference no less than eight hours of previous urine.

Once urine samples were received, added them, for conservation, 0.1 g of ascorbic acid per 10 mL of urine, and stored at -70°C until it´s quantification.

For the analysis of the metabolites 2OHE1 and 16αOHE1, was used a competitive solid phase enzyme immunoassay method, using the commercial kit ESTRAMET™ 2/16 (Immune Care Corporation, Bethlehem, MI. USA), which was validated by the manufacturer by gas chromatography and mass spectrometry. The analysis was performed according to the manufacturer's instructions; briefly: the urine sample was hydrolyzed with an enzyme beta glucuronidase and sulfatase activities. The free urinary metabolites, joined to monoclonal antibodies conjugated with alkaline phosphatase. The quantification of metabolites 2OHE1 and 16αOHE1 were performed in triplicate and the reproducibility of this method has already been reported by our team in a study. For each of the determinations of the RMEU were reference curves, achieving a 97% of accuracy.

Adherence and side effects. In the first assessment is gave women a calendar to daily record consumption or omission of the supplement (active compound or placebo) as well as a series of side effects in order to assess the adherence and safety of supplement. This included side effects that had already been reported in other studies with DIM and I3C. In addition requested participants return the supplements vial to subsequently make the count of pills that were left over.

Sample size.

To estimate the sample size it was considered the following:

Two sets of comparison (Placebo and 75mg DIM). According to literature and hoping to find a difference of .48 in the average of RMEU of the group of supplementation relative to the placebo group.

Other studies have reported a standard deviation of .77 on the RMEU. Calculated with an alpha of 0.05 and a power of 80%. Approximately 31 women are required by group plus 10% to replace losses in the follow-up, which gives an approximate total of 35 women per group.

Statistical Analysis. The statistical analysis of data was carried out in the following way: the differences between baseline characteristics was performed using the student T test for parametric variables with normal distribution, U Mann-Whitney for those who did not have a normal distribution and X2 for the nonparametric. The change of estrogen metabolites and RMEU in each group was evaluated using the Wilcoxon test and the comparison of the effect between groups, the values of concentrations of the metabolites of estrogen and the RMEU as well as their differences, was carried out by means of the test U Mann-Whitney.

Masking. A stranger to the study researcher, received and coded vials containing the DIM supplement and placebo, recording the code in a role that was kept in an envelope that was opened at the end of the study.

Effectiveness of DIM Supplements to Increase 2-OHE1/16 Ratio

Effectiveness of DIM Supplements to Increase 2-OHE1/16 Ratio in Premenopausal Mexican Women With Risk of Breast Cancer

First pregnancy after 35 years or no living children

Have at least one first-degree or second degree family, who has had or have the disease

According to the committee of socioeconomic levels of the Mexican Association of Market Research Agencies and Public Opinion (AMAI)

Number of portions per day (1 cup raw or 1/2 cup cooked) of any cruciferous vegetables

A schedule was provided to the patients to record the daily intake of the supplement DIM/placebo

A schedule was provided to the patients to record daily the presence of side effects that have been reported in other studies such as diarrhea, nausea , vomiting , headache and flatulence.

Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes

Researcher in Medical Sciences B

Hypersensitivity

Central Nervous System Stimulants

Tin Fluorides

Nicotine

Varenicline

Nicotinic Agonists

Cholinergic Agents

Neurotransmitter Agents

Varenicline dosing follows the recommended 12 week course: 0.5 milligram mg/day by mouth for Days 1-3, 0.5 mg twice a day for Days 4-7, and 1 mg twice a day thereafter. Participant takes Varenicline 1-10 days after Visit 1.

Starting on Day 8, and then every day after that, participant applies 1 placebo patch each day.

Questionnaire completion 1 to 10 days before first study drug/placebo dose and on Days 8, 17, 24, 31, 38, 52, and 73. On Days 17, 24, 38, and 73, done over the phone.

Counseling sessions performed on Days 8, 17, 24, 31, 38, 52, and 73. On Days 17, 24, 38, and 73, done over the phone. During counseling on Day 8, participant sets a "quit date" for stopping smoking for about 1 week after participant starts taking the study drug/placebo. Some of the counseling sessions may be recorded by video and/or audio tape.

Study staff calls participant 1 day before quit date and 3 days after quit date to check on progress in quitting smoking.

Participant takes placebo tablet 1-10 days after Visit 1. On Days 1-3, participant takes 1 dose of the placebo each morning. Starting on Day 4, and then every day after that, participant takes 1 dose in the morning and 1 dose in the evening.

Starting on Day 8, and then every day after that, participant applies 1 nicotine patch.

Questionnaire completion 1 to 10 days before first study drug/placebo dose and on Days 8, 17, 24, 31, 38, 52, and 73. On Days 17, 24, 38, and 73, done over the phone.

Counseling sessions performed on Days 8, 17, 24, 31, 38, 52, and 73. On Days 17, 24, 38, and 73, done over the phone. During counseling on Day 8, participant sets a "quit date" for stopping smoking for about 1 week after participant starts taking the study drug/placebo.

Study staff calls participant 1 day before quit date and 3 days after quit date to check on progress in quitting smoking.

Varenicline Dosing: 0.5 mg/day by mouth for Days 1-3; 0.5 mg twice a day for Days 4-7, and 1 mg twice a day thereafter.

Starting on Day 8, and then every day after that, participant applies 1, 21 mg nicotine patch for 11 weeks.

Nicotine Patch

Starting on Day 8, and then every day after that, participant applies 1 placebo patch each day for 11 weeks.

Placebo Patch

Participant takes placebo tablet 1-10 days after Visit 1. On Days 1-3, participant takes 1 dose of the placebo each morning. Starting on Day 4, and then every day after that, participant takes 1 dose in the morning and 1 dose in the evening.

Placebo Tablet

Questionnaire completion 1 to 10 days before first study drug/placebo dose and on Days 8, 17, 24, 31, 38, 52, and 73. Questionnaires should take about 30-45 minutes total to complete. On Days 17, 24, 38, and 73, done over the phone.

Questionnaires

Counseling sessions performed on Days 8, 17, 24, 31, 38, 52, and 73. On Days 17, 24, 38, and 73, done over the phone. These sessions take about 15 minutes each time.

Counseling Sessions

Participant asked to watch slides. During the lab session, brain electrical activity checked with an electroencephalogram (EEG). Participant completes computer tasks, including questionnaires, that will measure emotions and attention level. These tasks should take about 90 minutes to complete. The lab session may last up to 2 hours.

Lab Session

Saliva tested to check cotinine level at baseline, on Days 8 and 17, end of treatment visit, and at 3 months and 6 months after quitting smoking.

Saliva Test

Paul Cinciripini, PHD, MS, BS

The goal of this clinical research study is learn if varenicline or the nicotine patch can help people with different types of emotion and attention levels to quit smoking.

Study Groups:

If you agree to take part in this study, you will be randomly assigned (as in the roll of a dice) to 1 of 2 study groups. This is done because no one knows if one study group is better, the same, or worse than the other group. You will have an equal chance of being assigned to Group 1 or 2.

* If you are in Group 1, you will receive varenicline and a placebo patch. A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.
* If you are in Group 2, you will receive an active nicotine patch and a placebo tablet.

Neither you nor the study doctor will know which group you are assigned to. However, if needed for your safety, the study staff will be able to find out what you are receiving (called "unblinding").

Once the study has ended and the Data Safety Monitoring Board (DSMB) at MD Anderson has granted approval, you may be unblinded at your request.

Study Drug Administration:

You will start taking your assigned study drug(s) the day after Visit 1.

You should take varenicline/placebo tablets by mouth with a cup (8 ounces) of water after eating a full meal. On Days 1-3, you will take 1 dose of the study drug each morning. Starting on Day 4, and then every day after that, you will take 1 dose in the morning and 1 dose in the evening (for a total of 2 doses of the study drug each day). You must return any study drug bottles as well as any unused study drug to the study staff at each study visit.

You should apply the nicotine/placebo patch to the upper arm. You should put it in a slightly different place each day to avoid skin irritation. You may take the patch off at night to avoid sleeping problems.

You will be given a study diary to record how many cigarettes you smoke (if any) each day while you are on study.

You must return your study diary and any unused study drugs, patches, and/or containers at each study visit.

Study Visits (Visits 1-7):

At every study visit:

* You will complete questionnaires about several topics, including depression, suicide, your smoking behavior, and any effects from the study drug. These questionnaires should take about 30-45 minutes in total to complete.
* You will be giving the opportunity to complete the questionnaires verbally with a study staff member (either on phone or in person depending on the visit number) or electronically on your computer using a website administered by an online survey development company called Qualtrics.
* You will receive counseling about quitting smoking, where you will talk about possible "triggers" for smoking and strategies for dealing with quitting smoking. These sessions will take about 15 minutes each.

At Visits 1, 4 and 6:

* Urine or saliva will be collected for a routine test to check your cotinine, nicotine, and anabasine levels. Cotinine is a chemical released in your body when it breaks down nicotine and will show whether and how much you have recently smoked. Anabasine is used to show if nicotine is found in the blood due to a nicotine replacement therapy or from tobacco use.
* Your CO level and weight. will be measured.
* If you did not have one during screening, you will have a physical exam.
* If you did not complete at one during screening or before Visit 1, you will complete the EEG/lab session.
* If you can become pregnant, urine will be collected for a pregnancy test.
* At V1, if your CO machine tests results are unclear, and the study staff thinks it is appropriate, a NicAlert test will be performed. Urine will be collected for the NicAlert test, which is more sensitive at detecting levels of smoking than the CO machine.

During counseling on Day 8, you will set a "quit date" for stopping smoking for about 1 week after you start taking the study drug/placebo. You should not quit smoking before the quit date. You may also set goals to reduce smoking. You should try to stay smoke-free after the quit date. You will also be given a drug instruction sheet, a card with emergency contact information, and a participant manual to help you follow along with the topics discussed during counseling.

Visits 2, 3, 5 and 7 will be conducted over the phone. You will complete questionnaires about several topics (either on the phone or electronically), including depression, mood, your smoking behavior, and any effects from the study drug. You will also be asked about any drugs you may be taking. Each call should take about 25-45 minutes.

The study staff will call you 1 day before your quit date and 3 days after your quit date to check on your progress in quitting smoking. Each call should take about 10-15 minutes.

Lab Session:

You will take part in a lab session at or before Visit 1 to test your brain activity. You will be asked to watch slides. The slides will include pictures of people, nature, and artwork. Slides showing nude people, medical procedures, and victims of car crashes will also be shown. You will be shown examples of these slides before beginning the procedure and given the opportunity to withdraw from the study.

During the lab session, your brain electrical activity will be checked with an electroencephalogram (EEG). To do this, small sensors will be placed on your scalp and face. You should not drink more than 2 cups of coffee or other caffeinated drinks for at least 2½ hours before the session. At the lab session, you may be asked to smoke a cigarette if the doctor thinks it is needed for you to show your normal smoking behavior.

You will also complete computer tasks, including questionnaires that will measure your emotions and attention level. These tasks should take about 90 minutes to complete.

The lab session may last up to 2 hours.

Ecological Momentary Assessments (EMA):

EMA are used to gather information about your mood and cravings as they happen in your day-to-day life. At your randomization visit, you will be loaned a smart phone device, and will be asked to complete questionnaires on the device at different times everyday throughout the active treatment phase (12 weeks). In these questionnaires, you will be asked about events from the previous day, such as cigarettes per day, alcohol intake, mood, sleep, motivation, and whether you took your prescribed drugs on time. These questionnaires should take up to about 20 minutes per day to complete.

Length of Treatment:

You will receive the study drug/placebo for up to 12 weeks. You will be taken off study early if the doctor thinks it is in your best interest or if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visits.

End-of-Treatment Visit (Visit 8):

After you have finished taking the study drug/placebo, the following tests and procedures will be performed:

* Your CO level will be measured.
* Blood (about 2 teaspoons) will be drawn to check your liver and kidney function.
* Urine or saliva will be collected to measure your nicotine, anabasine, and cotinine level.
* You will complete the same questionnaires you completed at the regular study visits.
* You will receive counseling about quitting smoking.
* If you can become pregnant, urine will be collected for a pregnancy test.

Follow-Up Visits (Visits 9 and 10):

At about 3 and 6 months after you have stopped smoking, the following tests and procedures will be performed:

* Your CO level will be measured.
* Urine or saliva will be collected to measure your nicotine, anabasine, and cotinine level.
* You will complete the same questionnaires you completed at the regular study visits.

This is an investigational study. Varenicline and the nicotine patch are both FDA approved and commercially available to help people stop smoking. The study doctor can explain how the study drugs are designed to work.

Up to 160 participants will be enrolled in this portion of the study. All will take part at MD Anderson.

Reward Sensitivity and Pharmacotherapy for Smoking Cessation

The Effects of Behavioral Counseling Plus Nicotine Replacement Therapy (NRT) or Varenicline on Smoking Cessation Among Smokers High and Low in Intrinsic Reward Sensitivity

Continuous abstinence over the last 4 weeks of treatment (i.e. EOT-end of treatment) will serve as the primary outcome measure. Saliva will be collected to measure cotinine level.

For prolonged abstinence, relapse defined by 7 or more consecutive days of smoking or smoking at least 1 cigarette over two consecutive weeks from the end of the grace period to a future time point (e.g., EOT, 3- and 6- months post-quit date).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Knee Pain	NCT01351805	Autoimmune Dise... Systemic Inflam... Knee Pain Chron... Osteoarthritis Rheumatoid Arth...	Fish Oil Vitamin D placebo pill	50 Years -	Brigham and Women's Hospital
Effectiveness of DIM Supplements to Increase 2-OHE1/16 Ratio	NCT02525159	Breast Cancer	DIM pills Placebo Pill	35 Years - 52 Years	Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes
Reward Sensitivity and Pharmacotherapy for Smoking Cessation	NCT02162849	Tobacco Use Ces...	Varenicline Nicotine Patch Placebo Patch Placebo Tablet Questionnaires Counseling Sess... Lab Session Saliva Test	18 Years - 75 Years	M.D. Anderson Cancer Center
Trial to Evaluate the Safety of Lovastatin in Individuals With Neurofibromatosis Type I (NF1)	NCT00352599	Neurofibromatos...	Lovastatin Lovastatin placebo pill	10 Years - 50 Years	University of California, Los Angeles
A Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract	NCT00894413	Head and Neck S...	Tadalafil Placebo Pill	18 Years - 99 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Reward Sensitivity and Pharmacotherapy for Smoking Cessation	NCT02162849	Tobacco Use Ces...	Varenicline Nicotine Patch Placebo Patch Placebo Tablet Questionnaires Counseling Sess... Lab Session Saliva Test	18 Years - 75 Years	M.D. Anderson Cancer Center
Efficacy of Propranolol Treatment to Prevent Melanoma Progression	NCT01988831	Stages III Skin... Stages II Skin ... Stage IB Skin M...	Propranolol hyd... Placebo pill	18 Years -	University Hospital, Geneva
A Trial of Tadalafil in Patients With Squamous Cell Carcinoma of the Upper Aero Digestive Tract	NCT00894413	Head and Neck S...	Tadalafil Placebo Pill	18 Years - 99 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for placebo pill

Every month we try and update this database with for placebo pill cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.