Neoplasms

Symptoms and General Pathology

All Conditions

Nutritional and Metabolic Diseases

Musculoskeletal Diseases

Rare Diseases

Neoplasm Metastasis

Obesity

Craniopharyngioma

Adamantinoma

Ameloblastoma

Overweight

Overnutrition

Nutrition Disorders

Body Weight

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Bone Neoplasms

Bone Diseases

Hypothalamic Obesity

Neuroepithelioma

Hypoglycemic Agents

All Drugs and Chemicals

Antihypertensive Agents

Vasodilator Agents

Insulin

Insulin, Globin Zinc

Metformin

Diazoxide

Diazoxide will be initiated at half the dose (100 mg per day) for 2 weeks to allow the insulin sensitizing action of metformin to take effect. Dosage will be increased to 200mg daily, divided twice daily with meals for 6 months.

Metformin will be initiated at 500 mg twice daily and increased to 1000 mg twice daily over a one week period to minimize gastrointestinal side effects. the 2000mg is to be taken with meals for 6 months.

Jill Hamilton, MD

To study the effect of combined diazoxide-metformin therapy on body weight in youth with hypothalamic obesity following treatment for craniopharyngioma. A secondary objective is to evaluate changes in insulin resistance (IR), beta-cell function, features of the metabolic syndrome, muscle metabolism and intramyocellular lipid.

Hypothesis: Treatment with diazoxide and metformin will result in weight loss or slowed weight gain and improved metabolic profile, compared to pretreatment levels.

46 children under the age of 22 years have been treated surgically for craniopharyngioma tumor and are currently followed at the Hospital for Sick Children, Toronto. Approximately 50% are obese (BMI ≥ 95th percentile for age and gender assessed from the updated Centre for Disease Control growth charts), all of whom have panhypopituitarism requiring hormone replacement therapy. These children are assessed regularly in Endocrine Clinic and also are invited to attend a comprehensive care clinic for evaluation by an endocrinologist (Principal Investigator), neurosurgical clinical nurse practitioner, dietitian, exercise physiologist, psychologist and social worker to provide multi-disciplinary dietary and exercise consultation and psychological counseling for weight related concerns. This clinic will provide the infrastructure for recruitment and follow-up of study patients. Recruitment of eight subjects for this pilot study will occur over 6 months from patients attending the comprehensive clinic. This number was chosen as it is equivalent to the number chosen in the pilot study of octreotide by Lustig which showed beneficial changes in body mass index with treatment.

This study evaluates a novel combination therapy in children with hypothalamic obesity at very high risk for complications. Evaluation of insulin resistance and metabolic changes on therapy will allow a better understanding of how insulin secretion relates to weight gain in this population. Successful therapy in a pilot setting will provide necessary data for a larger randomized trial in individuals with hypothalamic obesity including children with craniopharyngioma and others with damage to the hypothalamus secondary to other tumors, surgery or cranial irradiation.

Hypothalamic Obesity Following Craniopharyngioma Surgery: A Pilot Trial of Combined Metformin and Diazoxide Therapy

Combined Diazoxide and Metformin Therapy in Children With Hypothalamic Obesity Secondary to Craniopharyngioma: A Pilot Study

The Hospital for Sick Children

Staff Endocrinologist

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Syndrome

Polycystic Ovary Syndrome

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

Micronutrients

Other Dietary Supplements

Inositol

100mg orally three times per day for 10 days

diazoxide

John E. Nestler, MD

Increased insulin levels leads to increased secretion of D-chiro inositol(DCI) from the kidneys in women with PCOS, but not in normal women. This leads to a reduction in circulating DCI and insulin stimulated release of DCI-IPG.To determine if decreasing circulating insulin directly by inhibition of islet insulin release with diazoxide in obese women with PCOS 1)decreases the renal clearance of DCI and 2) increases the circulating concentration of DCI.

Insulin and Polycystic Ovary Syndrome

Determination if Direct Inhibition of Insulin Release With Diazoxide Decreases Renal Clearance of D-Chiroinositol (DCI) and Increases Circulating DCI in Obese Women With Polycystic Ovary Syndrome (PCOS)

Following inhibition of insulin release using diazoxide, measured renal clearance of D-chiro inositol (DCI) via urinary Chiro-inositol dci assay

Measured circulating concentration of plasma DCI following inhibition of insulin release using diazoxide

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Virginia Commonwealth University

PCOS subjects given diazoxide

diazoxide: 100mg orally three times per day for 10 days

PCOS Subjects

Normal subjects given diazoxide

diazoxide: 100mg orally three times per day for 10 days

Normal Subjects

Total

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

BMI (Body Mass Index)

Waist-to-hip ratio (WHR)

Sex hormone binding globulin (SHBG) (nmol/L)

Total testosterone (ng/mL)

Free testosterone (pmol/L)

Fasting glucose (mg/dl)

Fasting insulin (ulU/mL)

Area under the curve (AUC) glucose (mg*min/dL)

AUC insulin (mg*min/ml)

Whole Body Insulin Sensitivity Index

Plasma DCI (nmol/mL)

24-h urinary D-chiroinositol (DCI) (nmol/day)

Urinary clearance (uCl) DCI (ml/min)

Plasma myo-Inositol (MYO) (nmol/mL)

24-h urinary MYO (nmol/day)

uCI MYO (ml/min)

Obese women with and without PCOS between the ages of 18-40 years selected after examination and eligibility screening

Dr. John Nestler

Renal Clearance of D-chiroinositol (DCI) at 12 Days

Level of Circulating D-chiro Inositol (DCI)

Overall Study

Nervous System Diseases

Pituitary Diseases

Hyperinsulinism

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

DIAZOXIDE

Raja BRAUNER, MD,PhD

In children treated for intracranial lesions, the 2 factors of the obesity are : the location of the lesion (hypothalamic-pituitary region) and craniopharyngiomas

Approximately 80 % of the hypothalamic-pituitary lesions that occur in children are craniopharyngiomas with one or three cases per 1 million children each year.

One major problem remains unsolved : the obesity

This study is performed to optimize the management of the children with hypothalamic-pituitary lesions by reducing the hyperinsulinemia due to the lesion and the surgery

Effect of Diazoxide on the Obesity Secondary to Hypothalamic-pituitary Lesions

Clinical Assessment of the Treatment With Diazoxide in Children Suffering From Obesity and Hyperinsulinemia Secondary to Surgery of Hypothalamic-pituitary Lesions

Assistance Publique - Hôpitaux de Paris

Isabelle BRINDEL

Neuroendocrine Tumors

Hypoglycemia

Endocrine Gland Neoplasms

Neuroendocrine Tumor

Gastro-enteropancreatic Neuroendocrine Tumor

Pancreatic Neuroendocrine Tumor

Pasireotide

Hormones

Hormone Antagonists

Off label use of pasireotide to treat refractory hypoglycemia due to an insulin-producing pancreatic neuroendocrine tumor

Pasireotide will be used, in addition to diazoxide, as a medical treatment to blunt hypoglycemia in the setting of autonomous insulin secretion.

Kashif M Munir, MD

Pasireotide binds to somatostatin receptors sst2 and sst5, which can lead to significant hyperglycemia. The investigators would like to administer pasireotide as a treatment for refractory hypoglycemia in the setting of metastatic insulin-producing pancreatic neuro-endocrine tumor.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hypothalamic Obesity Following Craniopharyngioma Surgery: A Pilot Trial of Combined Metformin and Diazoxide Therapy	NCT00892073	Hypothalamic Ob...	Diazoxide Metformin	9 Years - 22 Years	The Hospital for Sick Children
Insulin and Polycystic Ovary Syndrome	NCT00683774	PCOS	diazoxide	18 Years - 40 Years	Virginia Commonwealth University
Insulin and Polycystic Ovary Syndrome	NCT00683774	PCOS	diazoxide	18 Years - 40 Years	Virginia Commonwealth University
Effect of Diazoxide on the Obesity Secondary to Hypothalamic-pituitary Lesions	NCT00306683	Hypothalamic-pi... Craniopharyngio...	DIAZOXIDE	6 Years - 18 Years	Assistance Publique - Hôpitaux de Paris
Pasireotide Treatment for Neuroendocrine Tumor	NCT02779257	Gastro-enteropa...	Pasireotide Diazoxide	18 Years - 75 Years	University of Maryland, Baltimore
Pasireotide Treatment for Neuroendocrine Tumor	NCT02779257	Gastro-enteropa...	Pasireotide Diazoxide	18 Years - 75 Years	University of Maryland, Baltimore

Spots Global Cancer Trial Database for diazoxide

Every month we try and update this database with for diazoxide 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.

Spots Global Cancer Trial Database for diazoxide

Every month we try and update this database with for diazoxide 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.

Every month we try and update this database with for diazoxide 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.