Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Hot Flashes

Breast Diseases

Skin Diseases

Menopause

Gastrointestinal Agents

All Drugs and Chemicals

Mineral

Magnesium Oxide

Antacids

Anti-Ulcer Agents

Magnesium Supplement

Patients receive a low-dose of magnesium oxide orally (PO) daily (QD).

Patients receive a high-dose of magnesium oxide PO QD.

Patients receive a low-dose of placebo PO QD.

Patients receive a high-dose of placebo PO QD.

magnesium oxide

placebo

Charles L. Loprinzi, MD

RATIONALE: Magnesium oxide may help relieve hot flashes symptoms in women with a history of breast cancer.

PURPOSE: This randomized clinical trial studies how well a high-dose or a low-dose of magnesium oxide works compared to placebo in treating menopausal women with hot flashes and a history of breast cancer.

OBJECTIVES:

Primary

* Evaluate the efficacy of magnesium oxide on hot flashes in women with a history of breast cancer.

Secondary

* Evaluate the side-effect profile of magnesium oxide in this study population.
* Evaluate the effect of magnesium oxide on the secondary outcomes hot flash frequencies, hot flash severities, toxicities (including diarrhea), and hot flash-related daily interference on activities.
* Evaluate the effect of magnesium oxide on the change of magnesium level (for the first 150 patients).

OUTLINE: This is a multicenter study. Patients are stratified according to age (18-49 years vs ≥ 50 years), current tamoxifen and/or selective estrogen receptor modulator (yes vs no), current aromatase inhibitor (yes vs no), and daily frequency of hot flashes (4-9 vs ≥ 10). Patients are randomized to 1 of 4 treatment arms.

* Arm I: Patients receive a low-dose of magnesium oxide orally (PO) daily (QD).
* Arm II: Patients receive a high-dose of magnesium oxide PO QD.
* Arm III: Patients receive a low-dose of placebo PO QD.
* Arm IV: Patients receive a high-dose of placebo PO QD. In all arms, treatment continues for 8 weeks in the absence of unacceptable toxicity.

Some patients may continue or crossover to receive magnesium for 4 more weeks.

Patients complete the Hot Flash Diary daily for 9 weeks beginning 1 week before treatment. They also complete the Symptom Experience Questionnaire, the Profile of Mood States (POMS), and Hot Flash-Related Daily Interference Scale (HFRDIS) questionnaires periodically during study treatment.

Patients undergo blood sample collection at baseline and at the end of weeks 5 and 9 for serum magnesium level analysis.

Magnesium Oxide in Treating Postmenopausal Women With Hot Flashes and a History of Breast Cancer

A Randomized, Double-Blind, Placebo-Controlled Study of Magnesium Supplements to Reduce Menopausal Hot Flashes

The primary endpoint is the intra-patient changes of weekly hot flash activity from baseline during the treatment period. The hot flash activity will be measured by the weekly average hot flash score, which is a composite entity of both frequency and severity of hot flashes.

The hot flash severity is graded from 1 to 4 (1=mild, 2=moderate, 3=severe, and 4=very severe). The daily hot flash score is computed by multiplying the mean grade of severity by the frequency during every 24 hour period. Therefore, a score of zero is the lowest possible score and can be interpreted as having no hot flashes. The weekly hot flash score was calculated by adding all scores for the week.

The mean Hot Flash Score for each week for each group is reported and a repeated measures analysis is reported comparing each dose level group to the Placebo group.

As part of the Hot Flash Diary, the number of hot flashes was recorded for each patient for each week. For this endpoint, the mean number of hot flashes for each group is reported. A repeated measure analysis comparing each dose level group and the Placebo is reported.

Frequency and severity of adverse events reported by patients in weekly Symptom Experience Questionnaire and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report.

We will use the Symptom Experience Questionnaire (SEQ) to evaluate the specific impact of the study treatment on the effect hot flashes have on various life activities such as work, social, leisure and relationships. The questionnaire is 14 questions and is based on a 0="Not at all" to 10="As bad as it can be" scale. The change of severity of symptoms as measured by the SEQ from baseline to treatment termination will be first summarized by descriptive statistics as a percent change from baseline.

We will use the Hot Flash Related Daily Interference Scale (HFRDIS) (SEQ) to evaluate the specific effect of hot flashes have on various life activities such as work, social, leisure and relationships while receiving treatment. The questionnaire is 10 questions and is based on a 0="Do not interfere" to 10="Completely interfere" scale. The weekly score is the summation of these 10 questions and therefore ranges from 0 to 100. The total change in severity of symptoms is calculated by subtracting the week 8 score from the baseline. Therefore, values below zero indicate a worsening of symptoms and values above zero indicate an improvement and has a maximum range of -100 to 100. A gatekeeper procedure, following a fixed-sequence hypothesis testing method, was used to examine the higher dose of magnesium vs. placebo first and then the lower dose of magnesium vs. placebo, if the former was statistically significant.

The intra-patient changes of magnesium level from baseline to the end of treatment period between magnesium oxide and placebo arms will be compared using a repeated measures model.

Serum magnesium concentrations will be performed prior to study medication usage and during the last week of blinded study use. These will be obtained in the first 150 patients. Mean change in serum magnesium concentrations will be compared between the 3 study arms to determine whether there are any apparent changes in the patients receiving placebos vs the two magnesium doses.

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

All patients that began treatment and were assessed for adverse events (AEs) are reported. In the Low Dose arm, 97 patients were randomized, 5 were never assessed for AEs. In the High Dose arm, 96 patients were randomized, 3 patients were never assessed for AEs. In the placebo arms, 96 patients were randomized, 4 were never assessed for AEs. This leaves 92, 93, and 92 patients on Low Dose, High Dose and Placebo arms respectively assessed for Adverse events.

Week 2:

Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD).

Week 3:

Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).

Weeks 4-9:

Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).

Low Dose Magnesium Oxide (800 mg/Day)

Week 2:

Patients take one 400 mg tablet of magnesium oxide orally (PO) daily (QD).

Week 3:

Patients take two 400 mg tablet of magnesium oxide orally (PO) daily (QD).

Weeks 4-9:

Patients take three 400 mg tablet of magnesium oxide orally (PO) daily (QD).

High Dose Magnesium Oxide (1200 mg/Day)

Patients registered to the High Dose Placebo and Low Dose Placebo are combined for treatment analysis.

Week 2:

Patients take one placebo tablets orally (PO) daily (QD).

Week 3:

Patients take two placebo tablets daily (QD).

Weeks 4-9:

Patients take two or three placebo tablets daily (QD).

Placebo

After the double blind phase patient questionnaire booklet has been completed and returned to the investigator, the patient will be told whether she was on magnesium or placebo. If the patient wishes to continue or start the magnesium, and healthcare provider approves that this is an appropriate option, she may be registered on the Optional Continuation Phase of the study. This phase will last up to 4 weeks of treatment following either 800 or 1200 mg/day treatment group.

Optional Continuation Phase

Total

Age Group

Age, Customized

Sex: Female, Male

United States

Region of Enrollment

Charles Lawrence Loprinzi, M.D.

Baseline

Week 1

Week 2

Week 3

Week 4

Week 5

Week 6

Week 7

Week 8

All patients that began protocol treatment and completed the Hot Flash Diary were included in this analysis.

The Intra-patient Changes of Weekly Hot Flash Activity From Baseline During the Treatment Period.

Weekly Frequency of Hot Flashes as Measured by the Hot Flash Diary During the Treatment Period

Grade 3+ Adverse Event

Grade 4+ Adverse Event

All patients that started protocol treatment and were evaluated for adverse events are included in this analysis.

Frequency and Maximum Grade of Adverse Events Reported Via the CTCAE 4.0 During the Treatment Period.

Stomach Pain

Diarrhea

Nausea

Dizziness

Decreased Appetite

Fatigue

Muscle Weakness

Abnormal Sweating

Constipation

Muscle/Joint Aches

Trouble Sleeping

Negative mood change

Trouble Concentrating

Distress

All patients that started treatment and completed the Symptom Experience Questionnaire at baseline and Cycle 9 were included in this analysis.

The Change of Severity of Symptoms as Measured the Symptom Experience Questionnaire From Baseline to Treatment Termination

All patients that began treatment and completed the HFRDI questionnaire at baseline and week 8 were used in this analysis.

The Change of Daily Interference as Measured by the Hot Flash Related Daily Interference Scale (HFRDIS) From Baseline to Treatment Termination.

All patients that started protocol treatment and had serum magnesium levels obtained at baseline and week 9 were included in this analysis.

The Intra-patient Changes of Magnesium Level From Baseline to the End of Treatment Period Between Magnesium Oxide and Placebo Arms.

Week 2:

Patients take one placebo tablets orally (PO) daily (QD).

Week 3:

Patients take two placebo tablets daily (QD).

Weeks 4-9:

Patients take two placebo tablets daily (QD).

Low Dose Placebo

Week 2:

Patients take one placebo tablets orally (PO) daily (QD).

Week 3:

Patients take two placebo tablets daily (QD).

Weeks 4-9:

Patients take three placebo tablets daily (QD).

High Dose Placebo

Double-Blind Treatment Phase

Patients receive magnesium oxide by mouth daily or twice daily for 4 weeks.

questionnaire administration

quality-of-life assessment

Thomas J. Smith, MD

RATIONALE: Magnesium oxide may help relieve hot flashes in women with cancer.

PURPOSE: This phase II trial is studying how well magnesium oxide works in treating hot flashes in menopausal women with cancer.

OBJECTIVES:

Primary

* To determine if magnesium oxide supplement will decrease the frequency and severity of hot flashes by 50% in menopausal women with cancer.

Secondary

* To evaluate the effect of magnesium oxide on overall quality of life.
* To evaluate the toxicities of magnesium oxide when administered at commonly used supplement doses.

OUTLINE: Patients receive oral magnesium oxide once daily in weeks 2-5. Patients whose hot flashes are not satisfactorily controlled after 2 weeks of treatment may receive magnesium oxide twice daily in weeks 4 and 5.

Patients complete a daily hot flash diary for 5 weeks beginning 1 week before treatment. Patients also complete quality-of-life, symptom, and self-assessment questionnaires at baseline, once weekly during treatment, and at the completion of treatment.

After completion of study treatment, patients are followed up for at least 30 days.

Magnesium Oxide in Treating Hot Flashes in Menopausal Women With Cancer

A Pilot Phase II Trial of Magnesium Supplements to Reduce Menopausal Hot Flashes in Cancer Patients

Hot flash score (frequency x severity) at baseline was compared to the end of treatment. The number of flashes in a 24 hour day and a score combining the number and severity of hot flashes (ie, 1 point for mild, 2 points for moderate, 3 points for severe and 4 points for very severe.

Mayo Clinic Uniscale instrument (6 questions with each question rating 0=as bad as it can be and 10=as good as it can be). A lower score is considered to be a better outcome.

Virginia Commonwealth University

Patients receive magnesium oxide PO QD or BID for 4 weeks.

Supportive Care (Magnesium Oxide)

Age, Categorical

Age, Continuous

25 patients completed the complete study and were analyzed

Percent Difference in Hot Flash Activity (Score) Between Baseline and End of Treatment (Week 5)

Difference in Quality of Life

Overall Study

Nutritional and Metabolic Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Syndrome

Overweight

Polycystic Ovary Syndrome

Insulin Resistance

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Hypoglycemic Agents

Insulin

Insulin, Globin Zinc

Hormones

magnesium tablets, 250 milligram magnesium, 8 weeks, every day 1 tablet

Placebo tablets, the same in color, odor and appearance with magnesium tablets, 8 weeks, one tablet every day

This is a double-blind randomized clinical trial which will be started at June 2014 and end on June 2015 in Isfahan city. Serum insulin level is considered as a key variable and the sample size was calculated to be 70 persons (35 persons for control group and 35 persons for patient group). Patient group will receive magnesium supplement (250 milligram) and the other group will receive placebo which is similar to the magnesium tablets in color, odor and appearance both for 8 weeks. All subjects will complete 4 physical activity and 4 dietary records. Outcome measurements including metabolic and inflammatory profiles,sex hormone levels will be measured at the beginning and end of the study as well as anthropometric measurements.

Ahmad Esmaeilzadeh, Professor

maryam farsinejadmarj, Bachelor

Ahmad Esmaeilzadeh, professor

This is a double-blind randomized clinical trial which will start at June 2014 and end on June 2015 in Isfahan city. Serum insulin level is considered as a key variable and the sample size calculated 70 persons (35 persons for control group and 35 persons for patient group). Patient group will receive magnesium supplement (250 milligram) and the other group will receive placebo which is similar to the magnesium tablets in color, odor and appearance both for 8 weeks. All subjects will complete 4 physical activity and 4 dietary records. Outcome measurements including sex hormone levels, metabolic and inflammatory profiles will be measured at the beginning and end of the study as well as anthropetric measurements.

Effect of Magnesium Supplementation on Polycystic Ovary Syndrome

Effect of Magnesium Supplementation on Metabolic Profile and Sex Hormone Levels in Overweight Women With Polycystic Ovary Syndrome.

Isfahan University of Medical Sciences

Associate Professor

Anticoagulants

Other Dietary Supplements

Citric Acid

Sodium Citrate

Magnesium citrate

Laxatives

Cathartics

Citrate

Participants will be given standard dose levels of Magnesium oxide according to the level of magnesium in blood.

Participants will be given standard dose levels of Magnesium citrate according to the level of magnesium in blood.

Magnesium Citrate

Michael Vickers, Dr.

Hypomagnesemia (hMg) is a common side effect of important anti-cancer therapies such as epidermal growth factor receptor inhibitors (EGFRIs) and platinum-containing anti-cancer drugs. EGFRIs, including cetuximab (cmab) and panitumumab (pmab), have been estimated to cause hMg in over 18% and 27% of patients respectively1, while 90% of patients receiving cisplatin will develop hMg if left untreated. The development of severe hMg may result in increased symptoms such as fatigue, neuromuscular changes, mental status changes and cardiac arrhythmias which could result in treatment delays and may compromise treatment efficacy. Despite the common occurrence of this toxicity, little is known regarding the optimal magnesium management strategy. As physicians do not know what the "best" treatment for patients is, genuine uncertainty ("clinical equipoise") exists. Physicians will choose between different "standards" of magnesium replacement in their personal practice, using idiosyncratic decision making processes, without the physician or the patient knowing the optimal option. This is not good for patients, physicians and society as a whole. Determining the optimal treatment remains an important medical issue for patients, physicians and society. This study will use a novel method to allow comparisons of established standard of care prophylactic treatment using the "integrated consent model" as part of a pragmatic clinical trial7. By integrating medical and clinical practices, physicians will be able to inform their patients about the randomized control trial, akin to a typical conversation between the physician and patient, without written informed consent. This clinical interaction would then be documented, as ordinarily done in practice. Medical and clinical practice will be intertwined with the patients' welfare at the forefront of our best interests.

Feasibility of Using an Integrated Consent Model to Compare Two Standard of Care Regimens for the Management of Hypomagnesemia From Anti-Cancer Therapies

Compare the differences in levels of magnesium between the two regimens

Determine whether systemic therapy-induced hypomagnesemia poses a serious risk of cardiac arrhythmias as measured by changes in average QTc intervals with changes in magnesium levels.

Determine cost differences between two magnesium replacement strategies.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Magnesium Oxide in Treating Postmenopausal Women With Hot Flashes and a History of Breast Cancer	NCT01439945	Breast Cancer Cancer Survivor Hot Flashes	magnesium oxide placebo	18 Years -	Alliance for Clinical Trials in Oncology
Magnesium Oxide in Treating Hot Flashes in Menopausal Women With Cancer	NCT01008904	Breast Cancer Cancer Survivor Hot Flashes Unspecified Adu...	magnesium oxide questionnaire a... quality-of-life...	18 Years -	Virginia Commonwealth University
Effect of Magnesium Supplementation on Polycystic Ovary Syndrome	NCT02178150	Polycystic Ovar...	Magnesium Oxide Placebo	20 Years - 45 Years	Isfahan University of Medical Sciences
Feasibility of Using an Integrated Consent Model to Compare Two Standard of Care Regimens for the Management of Hypomagnesemia From Anti-Cancer Therapies	NCT02690012	Hypomagnesemia	Magnesium Oxide Magnesium Citra...	19 Years -	Ottawa Hospital Research Institute
Magnesium Oxide in Treating Hot Flashes in Menopausal Women With Cancer	NCT01008904	Breast Cancer Cancer Survivor Hot Flashes Unspecified Adu...	magnesium oxide questionnaire a... quality-of-life...	18 Years -	Virginia Commonwealth University
Magnesium Oxide in Treating Hot Flashes in Menopausal Women With Cancer	NCT01008904	Breast Cancer Cancer Survivor Hot Flashes Unspecified Adu...	magnesium oxide questionnaire a... quality-of-life...	18 Years -	Virginia Commonwealth University
Effect of Magnesium Supplementation on Polycystic Ovary Syndrome	NCT02178150	Polycystic Ovar...	Magnesium Oxide Placebo	20 Years - 45 Years	Isfahan University of Medical Sciences
Magnesium Oxide in Treating Hot Flashes in Menopausal Women With Cancer	NCT01008904	Breast Cancer Cancer Survivor Hot Flashes Unspecified Adu...	magnesium oxide questionnaire a... quality-of-life...	18 Years -	Virginia Commonwealth University

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