Weight Gain
Conditions
Keywords
antipsychotic, metformin, children, adolescents
Brief summary
The purpose of this pilot study is to determine whether starting metformin in conjunction with a second-generation antipsychotic (SGA) and providing information about healthy eating and activity will prevent or reduce the amount of weight gain and the metabolic changes in adolescent youth typically seen with second-generation antipsychotic medication.
Detailed description
This is a 24 week, placebo-controlled, random assignment pilot study in which participants will be randomized in a 1:1 ratio to receive either flexible-dose treatment with metformin for 6 months as well as a newly initiated second generation antipsychotic medication or to receive placebo and the newly initiated antipsychotic medication. All subjects will also be provided healthy lifestyle instruction. The study involves monthly visits for the duration of the study. Participants may be treated as inpatients or outpatients throughout the course of the study. Participants will receive a psychiatric evaluation, physical exam, lab work, ECG, medication treatment, and psychiatric care. The goal is to evaluate the safety and efficacy of means to prevent and treat weight gain and the associated endocrine, metabolic, and inflammatory changes caused by antipsychotic medications. Behavioral treatments to reduce weight gain and metabolic problems after weight gain has occurred have had little impact. Such interventions must be intensive and sustained over months, if not years to be effective. Although basic lifestyle instruction (diet and physical activity) should be the standard of care for all children and adolescents at risk for becoming overweight, pharmacologic interventions may be the best option for substantially augmenting behavioral approaches to weight management.
Interventions
DRUGmetformin
500mg tablets, 250mg to 2000mg/day, po, BID to TID, 26 weeks
DRUGplacebo
500/0mg tablets, 250-2000mg/day divided BID to TID, po, 26 weeks
Sponsors
Foundation of Hope, North Carolina
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subjects will be between the ages of 10 and 17, male or female, any race or ethnicity * Any SPMI pediatric diagnosis that meets DSM-IV criteria and frequently is treated with a SGA- typically but not limited to psychotic, mood, pervasive developmental, oppositional defiant, and conduct disorders * SGA-naïve or less than 2 weeks exposure to any SGA, except ziprasidone * Legal guardian able and willing to give written informed consent * If competent, subject able and willing to assent for their own participation
Exclusion criteria
* Previous trial of metformin * Recommendation for treatment with clozapine or ziprasidone * Current use of insulin or any oral hypoglycemic agent * Current use of a medication known to mitigate weight gain - amantidine, histamine (H2) antagonists (cimetidine, ranitidine, nizatidine), topiramate, orlistat, sibutramine, stimulants (dextroamphetamine, methylphenidate) * Any current or past diagnosis of an eating disorder * Diabetes mellitus * Current active thyroid (TSH \>18 microIU/ml; T4 total \>18 mcg/dl), hepatic (2 LFTs \>4x upper limits of normal), renal (serum Creatinine \>1.4 mg/dL in females and serum Creatinine \>1.5 mg/dL in males), cardiac, gastrointestinal, or adrenal disease * Current substance abuse/dependence within past 2 weeks; a positive urine tox screen at baseline in the absence of meeting criteria for abuse/dependence will not preclude enrollment. * Pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Body Mass Index (BMI) | 0-24 weeks | Change in BMI-Body Mass Index (BMI) is a measure of body fat based on height, weight,gender and chronological age. Change in BMI is calculated as 24 weeks BMI minus the baseline BMI. |
| Change From Baseline to Week 24 in Weight | 24 weeks | Change in weight is calculated as 24 weeks weight minus the baseline weight. |
| Change From Baseline to Week 24 in Fat Mass | 24 weeks | Fat mass is a measure of excess body fat. Change in Fat Mass is calculated as 24 weeks fat mass minus the baseline fat mass. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Insulin Level | 24 weeks | Insulin is a peptide hormone and regulates carbohydrate and fat metabolism in the body.Change in Insulin level is calculated as the 24 weeks insulin level minus the baseline insulin level. |
| Incidence of Metabolic Syndrome | 24 weeks | Metabolic syndrome is a combination of the medical disorders that, when co-occurring, increase the risk of developing cardiovascular disease and diabetes. |
| Change From Baseline to Week 24 in Cholesterol Level | 24 weeks | According to the lipid hypothesis, abnormal cholesterol levels are strongly associated with cardiovascular disease because these promote atherosclerosis.Cholesterol levels are measured in milligrams (mg) of cholesterol per deciliter(dL) of blood.Change in cholesterol levels is measured at 24 weeks minus the levels at baseline. |
| Change From Baseline to Week 24 in Triglycerides | 24 weeks | In the human body, high levels of triglyceride fats in the bloodstream have been linked to atherosclerosis and, by extension, the risk of heart disease and stroke. A change in triglycerides is calculated from 24 weeks minus baseline levels. |
Countries
United States
Participant flow
Recruitment details
The first subject was enrolled into the study in January 2007 and enrollment ended in June 2009. All participants came to the ASPIRE clinic for all study visits.
Pre-assignment details
The study sought to recruit participants who had minimal or no prior exposure to second generation antipsychotics and no previous treatment with metformin.
Participants by arm
| Arm | Count |
|---|---|
| Metformin metformin in doses from 250mg to 2000mg/day for 26 weeks | 5 |
| Placebo Matched placebo to metformin, doses between 250/0mg and 2000/0,g per day | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Metformin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 5 Participants | 9 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 14.25 years STANDARD_DEVIATION 2.754 | 14.20 years STANDARD_DEVIATION 1.643 | 14.22 years STANDARD_DEVIATION 2.048 |
| Region of Enrollment United States | 4 participants | 5 participants | 9 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 3 / 4 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 |
Outcome results
Primary
Change From Baseline to Week 24 in Body Mass Index (BMI)
Change in BMI-Body Mass Index (BMI) is a measure of body fat based on height, weight,gender and chronological age. Change in BMI is calculated as 24 weeks BMI minus the baseline BMI.
Time frame: 0-24 weeks
Population: All participants who took at least one dose of study treatment and had at least one post baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change From Baseline to Week 24 in Body Mass Index (BMI) | 1.620 kg/m^2 | Standard Error 1.25 |
| Placebo | Change From Baseline to Week 24 in Body Mass Index (BMI) | 1.800 kg/m^2 | Standard Error 0.5701 |
Primary
Change From Baseline to Week 24 in Fat Mass
Fat mass is a measure of excess body fat. Change in Fat Mass is calculated as 24 weeks fat mass minus the baseline fat mass.
Time frame: 24 weeks
Population: Only participants with complete data on fat mass at both baseline and 24 weeks were utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change From Baseline to Week 24 in Fat Mass | 4.770 kg | Standard Error 1.77 |
| Placebo | Change From Baseline to Week 24 in Fat Mass | 8.225 kg | Standard Error 1.58 |
Primary
Change From Baseline to Week 24 in Weight
Change in weight is calculated as 24 weeks weight minus the baseline weight.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change From Baseline to Week 24 in Weight | 6.138 kg | Standard Error 4.346 |
| Placebo | Change From Baseline to Week 24 in Weight | 10.45 kg | Standard Error 5.882 |
Secondary
Change From Baseline to Week 24 in Cholesterol Level
According to the lipid hypothesis, abnormal cholesterol levels are strongly associated with cardiovascular disease because these promote atherosclerosis.Cholesterol levels are measured in milligrams (mg) of cholesterol per deciliter(dL) of blood.Change in cholesterol levels is measured at 24 weeks minus the levels at baseline.
Time frame: 24 weeks
Population: Only participants with complete data on cholesterol levels at both baseline and 24 weeks were utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change From Baseline to Week 24 in Cholesterol Level | -4.250 mg/dl | Standard Error 17.07 |
| Placebo | Change From Baseline to Week 24 in Cholesterol Level | -31.00 mg/dl | Standard Error 15 |
Secondary
Change From Baseline to Week 24 in Insulin Level
Insulin is a peptide hormone and regulates carbohydrate and fat metabolism in the body.Change in Insulin level is calculated as the 24 weeks insulin level minus the baseline insulin level.
Time frame: 24 weeks
Population: Only participants with complete data on insulin levels at both baseline and 24 weeks were utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change From Baseline to Week 24 in Insulin Level | 1.550 microIU/ml | Standard Error 4.25 |
| Placebo | Change From Baseline to Week 24 in Insulin Level | 4.80 microIU/ml | Standard Error 2.6 |
Secondary
Change From Baseline to Week 24 in Triglycerides
In the human body, high levels of triglyceride fats in the bloodstream have been linked to atherosclerosis and, by extension, the risk of heart disease and stroke. A change in triglycerides is calculated from 24 weeks minus baseline levels.
Time frame: 24 weeks
Population: Only participants with complete data on triglyceride levels at both baseline and 24 weeks were utilized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change From Baseline to Week 24 in Triglycerides | -4.667 mg/dl | Standard Error 6.766 |
| Placebo | Change From Baseline to Week 24 in Triglycerides | -0.5 mg/dl | Standard Error 0.5 |
Secondary
Incidence of Metabolic Syndrome
Metabolic syndrome is a combination of the medical disorders that, when co-occurring, increase the risk of developing cardiovascular disease and diabetes.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin | Incidence of Metabolic Syndrome | 0 participants |
| Placebo | Incidence of Metabolic Syndrome | 0 participants |