Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Diabetes Mellitus

Adrenal Insufficiency

Weight Loss

Malnutrition

Body Weight

Nutrition Disorders

Central Nervous System Stimulants

All Drugs and Chemicals

Vasoconstrictor Agents

Respiratory System Agents

Antineoplastic Agents

Reproductive Control Agents

Epinephrine

Megestrol

Megestrol Acetate

Racepinephrine

Epinephryl borate

Megestrol acetatet 7.5 mg/kg/day orally (lemon-lime suspension) for 90 days.

Megstrol Acetate

Placebo (lemon-lime suspension) taken orally for 90 days.

Placebo

David Dix, MD

Beverly Wilson, MD

The purpose of this research study is to determine if megestrol acetate can be used as an appetite stimulant to improve weight gain in children with cancer and poor nutrition. The study design is a randomized, double blind, placebo controlled trial. Secondarily, we would like to determine what effect any improvement in weight has on body composition by DEXA scan. This includes whether the drug results in an increase in fat, fat-free mass, or both. If our patients gain weight we would like to know if it improves their quality of life. Finally, many children with cancer lose too much weight and require feeding to occur through a tube put down their nose into their stomach (NG feeding). The tube can be painful to put down and is uncomfortable when in. Some children may also require nutrition to be given into a vein (Total Parenteral Nutrition or TPN). We are trying to see if we can prevent these procedures from happening by having the subjects gain weight. This study will tell doctors if the drug truly works (or does not work) in children who are underweight.

Overview of the study phases Prior to the randomization phase, we will draw some blood work (1 teaspoon) with regular blood work to see if you/your child meet the final eligibility requirements. If the results are within normal limits, we will proceed on to the Randomization Phase. If the results are not within normal limits for your/your child's age, then you/your child will not be able to proceed with the study and we will pass these test results on to your regular oncologist.

Randomization Phase If you/your child agree to take part in this study you/your child will have an equal chance of receiving one of two possible liquids: Megace (7.5 mg/kg/day taken once in the morning) or the same amount of a placebo (a placebo is a substance that looks and tastes exactly like the real medicine, however it is an inactive substance that contains no drug). This assigning to the drug or the placebo is called randomization. Neither you nor your physician can choose or know which treatment you are receiving. This "blinding" is necessary to fairly test these drugs. In an emergency, your physician can immediately find out which of the drugs/treatments you are receiving.

Once randomized, you/your child will be given a supply of the drug or the placebo. Both the drug and the placebo are a lemon-lime flavored liquid. There are no pills or tablets to take. You/your child are to take the liquid by mouth in the amount prescribed once per day. You will take the liquid every day for 90 days (3 months). The liquid is to be taken half an-hour before breakfast.

Pre-treatment Information Collection Phase Before you/your child start taking the liquid, we will collect some initial information. This will include taking your/your child's weight and height. A dietitian will perform an assessment of you/your child's body composition using a tool called a caliper. This will briefly pinch the skin at the back of your/your child's arm. It will not hurt. The dietitian will also measure your/your child's upper arms using a tape measure.

A research nurse will ask a series of questions called a Quality of Life assessment. This will tell us about how you/your child feels before starting the study.

Afterwards, you/your child will have a scan called a DEXA (stands for Dual Energy X-Ray Absorptiometry) scan done to assess your/your child's body composition. A DEXA scan does not hurt but requires that you/your child lie still on the table while the scanner moves over you/your child. Like all scans, there is some radiation exposure. However, the total amount of radiation is very small (about half the radiation exposure of a normal chest xray). This should not cause any problem for you/your child.

We will also draw some additional blood (approximately 1 teaspoon) from your central line. You/your child will not have extra pokes for the purposes of this study.

Follow-up Phase You/your child will be followed closely by our team of doctors and dieticians during the 90 days you/your child are on the study. Follow-up will occur when you are normally scheduled to see your doctor. This can occur at either the Pediatric Oncology outpatient clinics or when you are admitted to the BC Children's Hospital (Vancouver) or Stollery Children's Hospital (Edmonton). You do not have to make special appointments for the purpose of this study.

We will watch your weight closely during the 3 months of the study. If you/your child lose an additional 15% from your/your child's baseline (starting) weight we will stop you taking the medication or placebo. You will then receive regular medical care. This may include starting tube feeding or TPN.

We will also take additional blood work at least every 2 weeks during the 3 months. This can be done through your/your child's central line at times when regular blood work is being drawn. Once a month our research nurse will contact you by phone to see how things are going and ask questions about possible side effects.

Study Conclusion Phase At the end of the study we will again collect all the information as we did in the Pre-treatment Information Collection Phase. This will include your/your child's weight, height, caliper and arm measurements as well as asking the same quality of life questions. You will then have a second DEXA scan done.

After 90 days you will be told whether you received the drug (Megace) or the inactive substance (Placebo).

The time commitment for you/your child to take part in this research should be minimal. Each DEXA scan (you/your child are asked to complete 2 DEXA scans during the study) will take approximately 1 hour. Each study nurse interview (3) should take approximately 10-15 minutes each time. The quality of life questions will be asked three times and take approximately 5-10 minutes each time to complete.

A Randomized Clinical Trial of Megestrol Acetate as an Appetite Stimulant in Malnourished Children With Cancer

A Randomized, Double Blind, Placebo-Controlled Trial of Megestrol Acetate as an Appetite Stimulant in Malnourished Children With Cancer

University of Alberta

University of British Columbia

Immune System Diseases

Neoplasms

Nervous System Diseases

Rare Diseases

Syndrome

Cushing Syndrome

Addison Disease

ACTH-Secreting Pituitary Adenoma

Pituitary ACTH Hypersecretion

Adenoma

Pituitary Diseases

Adrenal Gland Diseases

Endocrine System Diseases

Adrenocortical Hyperfunction

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pituitary Neoplasms

Endocrine Gland Neoplasms

Autoimmune Diseases

Cushing's Syndrome

Addison's Disease

ACTH-secreting Pituitary Adenoma

Hyperadrenalism

Anti-Inflammatory Agents

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Hormones

Glucocorticoids

Adrenocorticotropic Hormone

Melanocyte-Stimulating Hormones

beta-Endorphin

Patients with Adrenal Insufficiency established or newly diagnosed, under glucocorticoid replacement therapy.

patients with adrenocorticotropic hormone (ACTH)-dependent or ACTH-independent Cushing's Syndrome diagnosis during active disease (new diagnosis or recidivating) at enrollment.

Age-, sex- and BMI- matched patients referring to our center for diagnostic procedures not affected by Adrenal Insufficiency or Cushing's Syndrome.

patients and controls will undergo circadian gene expression (CLOCK, ARNTL) evaluation at baseline and after 1, 3 and 6 months

circadian gene expression evaluation

Andrea Isidori, MD,PhD

Andrea M Isidori, MD,PhD

This is a multicentric, prospective, intervention study on circadian genes expression in peripheral blood mononuclear cells as biomarkers of circadian rhythm derangement in patients affected by alterations of endogenous glucocorticoids secretion (Cushing's Syndrome during active phase, treatment and under remission and newly or on established glucocorticoid replacement therapy adrenal insufficiency)

This is an intervention, prospective, multicentric study.

Enrolled patients will undergo 4 visits:

* Adrenal insufficiency (AI) patients: patients affected by primary or secondary adrenal insufficiency, whether newly diagnosed or on established glucocorticoid therapy, will be evaluated at baseline and after one, three and six months.
* Cushing's Syndrome (CS) patients: patients affected by Cushing's Syndrome will be evaluated at baseline during active phase of the disease and one, three and six months after treatment or remission. Patients affected by Cushing's Syndrome who will require glucocorticoid replacement therapy after remission will be evaluated three and six months after remission and then three and six months after the eventual glucocorticoid replacement therapy withdrawal. CS treatment will be surgery or medical therapy according to guidelines. Timing of medical therapy administration will change during protocol according to circadian rhythms.

Age-, sex- and BMI- matched healthy controls will be enrolled. Patients and controls will undergo the same procedures at baseline and after 1, 3 and 6 months.

The primary outcome measure will be the evaluation of circadian genes CLOCK and Aryl Hydrocarbon Receptor Nuclear Translocator Like (ARNTL) expression in peripheral blood mononuclear cells (PBMC) compared to healthy controls.

Secondary Outcomes measures will be:

* Circadian genes expression assessment compared to healthy controls at 7:00-8:00 Ante Meridiem (AM) (before breakfast), 12:00 AM (before lunch), 3:00-4:00 Post Meridiem (PM) (after lunch), 7:00 PM (before dinner), 12:00 PM;
* Immune profiling compared to healthy controls by the quantification of peripheral blood mononuclear cells (PBMC) subpopulations assessed by flow cytometry at 7:00-8:00 AM (before breakfast), 12:00 AM (before lunch), 3:00-4:00 PM (after lunch), 7:00 PM (before dinner), 12:00 PM;
* Evaluation of inflammatory cytokines and adipokines production compared to healthy controls at 7:00-8:00 AM (before breakfast), 12:00 AM (before lunch), 3:00-4:00 PM (after lunch), 7:00 PM (before dinner), 12:00 PM;
* Circadian cortisol rhythm by serum and salivary dosage at 7:00-8:00 AM (before breakfast), 12:00 AM (before lunch), 3:00-4:00 PM (after lunch), 7:00 PM (before dinner), 12:00 PM;
* Sleep disturbances evaluation by The Pittsburgh Sleep Quality Index (PSQI) self reported questionnaire
* Evaluation of infectious diseases frequencies and severity compared to healthy controls. Infectious diseases will be evaluated by an adaptation of Infectious Diseases Questionnaire (GNC)
* Circadian blood pressure using ambulatory blood pressure monitoring blood pressure waves for a noninvasive estimation
* Quality of life using SF-36-Item Health Survey questionnaire
* Psychometric Evaluation using Beck Depression Inventory questionnaire
* Evaluation of sexual dysfunction using FSFI questionnaire in woman and IIEF questionnaire in man
* Evaluation of insuline resistance calculated with HOMA index
* Evaluation of body weight (kg)
* Evaluation of blood lipid profile

patients will undergo circadian genes evaluation in peripheral blood mononuclear cells

Clinical Study on Circadian Genes Dysregulation in Patients With Glucocorticoid Disorders

Change in relative expression circadian genes of CLOCK and ARNLT from baseline compared to healthy controls. After PBMC isolation by Ficoll-Plaque gradient, complementary DNA (cDNA) pool will be extracted and used as the template for subsequent Polymerase Chain Reaction (PCR) amplification in Real time PCR; Gene expression will be quantified as relative expression compared to housekeeping genes.

Change from baseline in relative expression and variations throughout the day of circadian genes (CLOCK and ARNTL) compared to healthy controls at 7:00-8:00 AM (before breakfast), 12:00 AM (before lunch), 3:00-4:00 PM (after lunch), 7:00 PM (before dinner), 12:00 PM. After PBMC isolation by Ficoll-Plaque gradient, cDNA pool will be extracted and used as the template for subsequent Polymerase Chain Reaction (PCR) amplification in Real time PCR; Gene expression will be quantified as relative expression compared to housekeeping genes.

Number of cells (number per mm3) of peripheral blood mononuclear cell subpopulations at 7:00-8:00 AM (before breakfast), 12:00 AM (before lunch), 3:00-4:00 PM (after lunch), 7:00 PM (before dinner), 12:00 PM

Circadian cortisol rhythm by serum and salivary dosage at 7:00-8:00 AM (before breakfast), 12:00 AM (before lunch), 3:00-4:00 PM (after lunch), 7:00 PM (before dinner), 12:00 PM.

Sleep disturbances will be evaluated by The Pittsburgh Sleep Quality Index (PSQI). This questionnaire contains 19 self-related questions which are combined to create 7 component scores with a range of 0-3 points (0:no difficulty, 3: severe difficulty). Global score is the result to the addition of all component scores with a range of 0-21 points (0:no difficulty, 21: severe difficulty).

Frequencies and severity of infectious diseases will be evaluated by modified Infectious Diseases Questionnaire (GNC).

This questionnaire includes questions on infectious diseases of upper and lower respiratory tract, gastrointestinal tract, skin and urogenital tract contracted during the previous 12 months. Questions investigate on the number and duration of infections, necessity of antibiotic or antifungal therapy, hospital stay and days of absence from work. Final score represents the frequency of infections. Moreover, some questions investigate possible susceptible or protective factors for infectious diseases: vaccinations, use of corticosteroids, concomitant diseases, previous appendectomy, tonsillectomy, adenoidectomy, splenectomy or thymectomy.

Circadian blood pressure will be evaluated using ambulatory blood pressure monitoring blood pressure waves for a noninvasive estimation

Quality of life will be evaluated by the Physical Component score and the Mental Component score of the self-administered questionnaire SF-36-Item Health Survey questionnaire.

This questionnaire measures eight scales: physical functioning, role physical, bodily pain, general health (physical component) and vitality, social functioning, role emotional, mental health (mental component).

Interpretation of the score will be the following: at each item of the questionnaire corresponds a percentage value (from 0% to 100%). The average of the single items constitutes the scale total percentage (from 0% to 100%); missing data are not considered during calculation. High score defines a more favorable health state.

Psychometric Evaluation will be evaluated using Beck Depression Inventory questionnaire. : a 21-item measure of depressive symptoms. Each answer is scored on a scale value (from 0 to 3 points). The global score is obtained adding all single scores, with a range of 0-63. Higher score constitutes worse burden of symptoms (0-13: minimal depression, 14-19: mild depression, 20-28: moderate depression, 29-63: severe depression).

Evaluation of sexual dysfunction will be evaluated in women using FSFI questionnaire. This is a 19-item questionnaire that covers six domains: desire, arousal, lubrication, and orgasm, satisfaction, and pain. The ranges of the domain scores are as follows: for desire 1.2 - 6.0, for arousal, lubrication, orgasm and pain 0 - 6.0 and for satisfaction 0.8 - 6.0. The higher scores of the six domains indicate better sexual functioning about that domain. The overall FSFI score is obtained by summing the six domain scores. The overall FSFI scores range from 2.0 to 36.0, with higher scores indicating better sexual functioning.

Evaluation of sexual dysfunction will be evaluated in men using IIEF questionnaire. The IIEF is an internationally validated test. It is used to assign a score of erectile dysfunction: severe score 1 to 10; moderate score 11 to 16; low to moderate score 17 to 21; Low score 22 to 25; no erectile dysfunction score 26 to 30

Measurement of HOMA index calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5.

Measurement of Total Cholesterol, LDL cholesterol, HDL cholesterol, Triglyceredes

Evaluation of Tumor Necrosis Factor alpha (TNFα), Transforming Growth Factor beta (TGF-β), Interferon gamma (IFN-γ), Leptin, Resistin, Adiponectin, Adipsin, Monocyte Chemoattractant Protein-1 (MCP-1), Serpin, C Reactive Protein (CRP), Interleukin 6 (IL-6), Interleukin 10 (IL-10) serum concentrations at 7:00-8:00 AM (before breakfast), 12:00 AM (before lunch), 3:00-4:00 PM (after lunch), 7:00 PM (before dinner), 12:00 PM

University of Roma La Sapienza

Associate Professor

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Dermatologic Agents

Hydrocortisone-17-butyrate

No hydrocortisone or other steroids are given before, during, and after the surgery, except that patients develop postoperative adrenal insufficiency. If a patient develops postoperative adrenal insufficiency, he/she needs to receive hydrocortisone treatment (20mg at 0800 and 20mg at 1600) for one month and then check the level of morning serum cortisol to decide if it is time to start the hydrocortisone taper program.

Normal saline

Hydrocortisone sodium succinate is given on the operation day (100mg at 0800 \& 100mg at 2000), the postoperative day 1 (100mg at 0800 \& 50mg at 2000), and the postoperative day 2 (25mg at 0800). Hydrocortisone (po.) is then given starting from the afternoon of postoperative day 2 (20mg at 1600 and 0800) to the end of the first postoperative week, and 20mg at 0800 during the second postoperative week. This is called the "hydrocortisone taper program". If a patient develops postoperative adrenal insufficiency, he/she needs to receive hydrocortisone treatment (20mg at 0800 and 20mg at 1600) for one month and then check the level of morning serum cortisol to decide if it is time to start the hydrocortisone taper program.

Bing Xing, MD

Xiaopeng Guo, MD

Wei Lian, MD

The investigators hypothesize that withholding hydrocortisone during the peri-operation in patients with pituitary adenomas whose hypothalamus pituitary adrenal axis are intact are safe.

Pituitary is the headquarters of the endocrine system of the body, secreting several hormones maintaining the normal function of the endocrine organs. After surgery, pituitary dysfunction is seen in a small proportion of patients, even in some patients resulting in severe consequence, i.e. adrenal insufficiency or pituitary crisis. Therefore, patients undergoing pituitary surgery have been usually given "stress dose" steroids whether their hypothalamus pituitary adrenal (HPA) axis are deficient or preserved.

Results of several retrospective studies showed that there was no significantly increase in postoperative adrenal insufficiency in no supplementation (of hydrocortisone) group than in supplementation group. Given the considerable side effects of using steroids, whether hydrocortisone administration is necessary for all patients with pituitary adenomas during peri-operation needs to be discussed.

For Chinese patients with pituitary adenomas except for those of Cushing's disease, hydrocortisone administration during the peri-operation is a routine practice. Peking Union Medical College Hospital is the China Pituitary Disease Registry Center. Here, the investigators aim to launch a single-center prospective randomized controlled trial to verify the hypothesis that withholding hydrocortisone during the peri-operation in patients with pituitary adenomas whose HPA axis are intact are safe.

Participants are assigned to one of two groups, whether using hydrocortisone or not during peri-operation, in parallel for the duration of the study.

Participant, investigator, and outcome assessors are all prevented from having knowledge of the interventions assigned to individual participants. Care provider knows the individualized interventions.

Hydrocortisone Use During Peri-operation for Pituitary Adenomas

Withholding Hydrocortisone vs Routine Use of Hydrocortisone During Peri-operation in Pituitary Adenoma Patients With Intact Hypothalamus-Pituitary-Adrenal Axis: Randomized Controlled Trial to Assess Safety and Complications

The individual participant data will be available upon reasonable requests to the study chair, Dr. Bing Xing, or the study director, Dr. Wei Lian.

A random reading of blood sugar level more than 200 mg/dL (11.1 mmol/L), or a reading after two hours (after OGTT) over 200 mg/dL (11.1 mmol/L) indicates diabetes mellitus.

Urine volume \> 300ml for more than 3h or \> 6 liter per day, specific gravity of urine \<1.003, and serum sodium levels \> 145 mmol/L indicate diabetes insipidus.

The level of Na+, K+, and Ca++ in the blood

Numbers of erythrocytes, leukocytes, neutrophils, lymphocytes, thrombocytes in the blood

Percentage of neutrophils, monocytes, lymphocytes of the leukocytes

Prothrombin time, activated partial thromboplastin time, and thrombin time

Deep venous thrombosis as detected by ultrasound

Decreased bone density, osteoporosis, fracture, acne, and infections.

Adrenal insufficiency: lower-than-normal serum cortisol level at 8 a.m., plus the following related symptoms, including serious fatigue, muscle weakness, decreased appetite, nausea, vomiting, diarrhea, low blood pressure, palpitation, and fever.

Peking Union Medical College Hospital

Adrenal Gland Neoplasms

Adrenal Cancer

Pharmaceutical Solutions

Micronutrients

Vitamins

Cosyntropin

Vitamin A

Retinol palmitate

Mitotane

Hormone Antagonists

Retinol

At 0800h to 0900h, a 25 mm plastic intravenous line will be inserted in an antecubital vein. Then, 1 μg/ml ACTH aliquot stock solution will be pushed through, followed by 5 ml physiologic saline (0.9%). Serum cortisol and salivary free cortisol will measured just before ACTH administration and 30 minutes later.

Cosyntropin stimulation test

Leonard Saiegh, MD

Leonard Saiegh

Michal Yeiches

In mitotane treated patients, serum cortisol cannot be used to diagnose hypoadrenalism, since mitotane increases cortisol binding globulin levels (CBG), artificially raising total cortisol. Salivary free cortisol (SC) is not affected by CBG alterations, and reflects the free serum cortisol.

In the current study, investigators will assess serum and SC responses during low-dose cosyntropin stimulation test in healthy volunteers, mitotane-induced hypoadrenal patients on steroid replacement therapy and in patients who suffer from hypoadrenlism caused from other etiology. Investigators will compare results between groups and try to demonstrate the superiority of SC in assessing adrenal function in mitotane treated patients.

80-90% of circulating cortisol is bound to cortisol binding globulin (CBG) or transcortin, whereas only 3-10% is in the free state. Salivary free cortisol (SC) is an index of plasma free cortisol. In previous studies it was shown that in low-dose cosyntropin stimulation test, SC increases significantly in normal but not in hypoadrenal patients. It was suggested that dynamic assessment of the SC response to ACTH may be particularly helpful whenever the measurement of serum cortisol is complicated by increased or decreased CBG levels.

Adrenocortical carcinoma (ACC) is a rare malignancy with a heterogeneous presentation and a variable but generally poor prognosis. Mitotane is the main drug for ACC treatment and it plays a role both in adjuvant treatment after complete resection and in recurrent, inoperable and/or metastatic ACC. Mitotane blocks adrenocortical steroid synthesis and also exerts a specific cytotoxic effect on adrenocortical cells. Mitotane induces adrenal insufficiency, requiring hydrocortisone replacement therapy. In mitotane treated patients, serum cortisol cannot be used to diagnose hypoadrenalism, since mitotane increases CBG levels, artificially raising total cortisol. SC is not affected by CBG alterations, and reflects the free serum cortisol and may be more accurate in diagnosing hypoadrenalism in mitotane treated patients.

In the current study, investigators will assess serum and SC responses during low-dose cosyntropin stimulation test in healthy volunteers, mitotane-induced hypoadrenal patients on steroid replacement therapy and in patients who suffer from hypoadrenlism caused from any other etiology. Investigators will compare results between groups and try to demonstrate the superiority of SC in assessing adrenal function in mitotane treated patients.

Salivary Free Cortisol Response to Cosyntropin Stimulation Test in Mitotane Treated Patients

Salivary free cortisol concentrations during intravenous low dose cosyntropin stimulation test..

Serum cortisol concentrations during intravenous low dose cosyntropin stimulation test.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Randomized Clinical Trial of Megestrol Acetate as an Appetite Stimulant in Malnourished Children With Cancer	NCT00439101	Malnourished Ch...	Megstrol Acetat... Placebo	- 18 Years	University of British Columbia
A Randomized Clinical Trial of Megestrol Acetate as an Appetite Stimulant in Malnourished Children With Cancer	NCT00439101	Malnourished Ch...	Megstrol Acetat... Placebo	- 18 Years	University of British Columbia
Clinical Study on Circadian Genes Dysregulation in Patients With Glucocorticoid Disorders	NCT04374721	Cushing Syndrom... Adrenal Insuffi... Cushing Disease Addison Disease	circadian gene ...	18 Years - 80 Years	University of Roma La Sapienza
A Randomized Clinical Trial of Megestrol Acetate as an Appetite Stimulant in Malnourished Children With Cancer	NCT00439101	Malnourished Ch...	Megstrol Acetat... Placebo	- 18 Years	University of British Columbia
Hydrocortisone Use During Peri-operation for Pituitary Adenomas	NCT04621565	Pituitary Adeno... Adrenal Insuffi... Surgery	Normal saline Hydrocortisone	18 Years - 70 Years	Peking Union Medical College Hospital
Salivary Free Cortisol Response to Cosyntropin Stimulation Test in Mitotane Treated Patients	NCT03083834	Adrenal Insuffi... Adrenal Cancer	Cosyntropin sti...	18 Years - 80 Years	Bnai Zion Medical Center

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