Combined Diazoxide and Metformin Therapy in Children With Hypothalamic Obesity Secondary to Craniopharyngioma: A Pilot Study
9 Years
22 Years
Both
Hypothalamic Obesity
Trial Information
Combined Diazoxide and Metformin Therapy in Children With Hypothalamic Obesity Secondary to Craniopharyngioma: A Pilot Study
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.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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)
Outcome Time Frame:
6 months prior to baseline, Baseline, 6 months after baseline
Safety Issue:
No
Principal Investigator
Jill Hamilton, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
The Hospital for Sick Children
Authority:
Canada: Health Canada
Study ID:
1000008879
NCT ID:
NCT00892073
Start Date:
May 2006
Completion Date:
January 2008
Related Keywords:
- Hypothalamic Obesity
- Craniopharyngioma surgery
- Hypothalamic Obesity
- Children
- Combined Diazoxide and Metformin
- Craniopharyngioma
- Adamantinoma
- Obesity
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