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

NCT00892073 | Completed Phase 2 DMC

• 2 other identifiers: 10000088799427-H1117-120C
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypothalamic Obesity

Keywords

Craniopharyngioma surgery; Hypothalamic Obesity; Children; Combined Diazoxide and Metformin

Outcome Measures

Primary Outcomes (1)

• Change in BMI and BMI SDS (calculated using for Disease Control formula - www.cdc.gov.doc) over 6 months of treatment compared to change in BMI and BMI SDS over 6 month 'run-in' period (prior to study start)

  6 months prior to baseline, Baseline, 6 months after baseline

Secondary Outcomes (6)

• Insulin secretion

  Baseline to 6 months

• Insulin resistance

  Baseline to 6 months

• Lipid profile

  Baseline to 6 months

• Adiponectin

  Baseline to 6 months

• Leptin

  Baseline to 6 months

Study Arms (1)

Diazoxide and Metformin Therapy

EXPERIMENTAL

Drug: Diazoxide; Drug: Metformin

Interventions

Diazoxide DRUG

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.

Also known as: Proglycem

Diazoxide and Metformin Therapy

Metformin DRUG

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.

Also known as: Novo-metformin

Diazoxide and Metformin Therapy

Eligibility Criteria

• Age: 9 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Craniopharyngioma at least one year following surgery
• Evidence of at least one other endocrinopathy of hypothalamic origin
• Stable hormone replacement therapy (with one or more of thyroxine hydrocortisone, DDAVP, sex steroids and GH)
• Obesity, defined as weight \>120% Ideal Body Weight (IBW) or BMI \> 27 kg/m2, with normal weight for height before tumour diagnosis and weight gain \>2SD above mean for age for 1 year following tumour treatment (41).
• Age 9 -22 years
• Minimum of 6 months of standard diet and exercise intervention (run-in period). This was chosen to allow a period of prospective measurements to establish individual baseline slope of change in BMI SDS prior to initiation of active treatment with diazoxide and metformin.

You may not qualify if:

• Contraindications for Metformin or Diazoxide use (history or evidence of cardiac, renal, or progressive hepatic disease , diabetes or hypoxic conditions)
• Pharmacologic doses of glucocorticoids or use of other medications known to affect glucose metabolism (e.g. beta-blockers, oral hypoglycemics)
• Growth hormone (GH) initiation in the preceding 6 months or planned initiation in the next 6 months (to rule out potential confounding effect of GH on weight / body composition and glucose metabolism).
• Use of other weight loss medications
• Inability of the family and/or patient to comply with study protocol
• Non English speaking

Sponsors & Collaborators

• The Hospital for Sick Children: lead

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Sexual Infantilism

Interventions

Diazoxide; Metformin

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Hypogonadism

Intervention Hierarchy (Ancestors)

Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines

Study Officials

• Jill Hamilton, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Endocrinologist

Study Record Dates

• First Submitted: April 30, 2009
• First Posted: May 4, 2009
• Study Start: May 1, 2006
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: November 17, 2017

Record last verified: 2017-11

Locations

CA (1)