Hypothalamic Obesity Following Craniopharyngioma Surgery: A Pilot Trial of Combined Metformin and Diazoxide Therapy
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Combined Diazoxide and Metformin Therapy in Children With Hypothalamic Obesity Secondary to Craniopharyngioma: A Pilot Study|
- 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) [ Time Frame: 6 months prior to baseline, Baseline, 6 months after baseline ] [ Designated as safety issue: No ]
- Insulin secretion [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
- Insulin resistance [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
- Lipid profile [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
- Adiponectin [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
- Leptin [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
- Features of the metabolic syndrome [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||May 2006|
|Study Completion Date:||January 2008|
|Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
|Experimental: Diazoxide and Metformin Therapy||
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.
Other Name: ProglycemDrug: Metformin
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.
Other Name: Novo-metformin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00892073
|The Hospital for Sick Children|
|Toronto, Ontario, Canada|
|Principal Investigator:||Jill Hamilton, MD||The Hospital for Sick Children|