Weight GainPhase 2ZACNCT00617058
Improving Metabolic Parameters of Antipsychotic Child Treatment With Ziprasidone, Aripiprazole, and Clozapine
A Phase 2 study testing metformin and healthy lifestyle intervention in people with Weight Gain, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the relative risks and benefits of two approaches to the control of weight gain and other negative side effects in children and adolescents on 2nd generation antipsychotics (SGA): Healthy lifestyle instruction (nutritional and physical activity surveillance and advice) +… Read more about this study
- Who is it for?
- Ages 10 to 17 years
- Conditions the study is for
- Weight Gain
- What is being tested?
- metformin and healthy lifestyle intervention
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Sep 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Ages 10 to 17 years (inclusive).
- Receiving treatment with ziprasidone, aripiprazole or clozapine for the past 56 days or longer.
- Clinically stable on current treatment regimen (see Rationales below).
- Stable dose of current psychotropic co-medications for at least 30 days.
- BMI increase of > 7% within 3 months OR a > 0.5 BMI z-score increase within the past 24 months while taking olanzapine, quetiapine or risperidone, with maintenance of the threshold level of weight gain.
- Lifetime diagnosis of a schizophrenia spectrum disorder (schizophrenia, schizoaffective disorder, psychotic disorder NOS), a bipolar spectrum disorder (bipolar disorder, bipolar disorder NOS), certain mood disorders (mood disorder NOS, major depressive disorder with psychotic features), or certain disruptive/aggressive disorders (conduct disorder, intermittent explosive disorder, autism spectrum disorder with history of clinically significant levels of disruptive behaviors as defined below) using DSM-IV criteria determined by clinical interview and K-SADS-PL.
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- Sexually active girls must agree to use an effective form of birth control or be abstinent.
- Principle caretaker is able to participate in study appointments as is clinically indicated.
- guardian and the child must agree (legally consent and assent) to participation.
Who cannot join
- Any medication that would significantly alter glucose, insulin or lipid levels. Prohibited medications will include, but are not limited to: insulin, steroids, topiramate, sibutramine, orlistat, metformin, amantadine, vitamin E (other than in standard multivitamins), antidiabetic drugs, HIV drugs.
- Major neurological disorder or medical illness that affects weight gain (e.g., unstable thyroid disease), requires a prohibited systemic medication or procedure (e.g., diabetes mellitus [insulin], chronic renal failure [steroids]) or that would prevent participation in physical activity in the healthy lifestyle program.
- Current active thyroid (TSH >18 microIU/ml), 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.
- Fasting glucose > 125 mg/dL on two occasions indicating need for prompt treatment for diabetes.
- Child meets DSM-IV criteria for substance abuse or dependence disorder within the past month, not including tobacco abuse or dependence • Current treatment with more than one antipsychotic medication.
- Current treatment with more than 5 total psychotropic medications (i.e., 4 psychotropics plus SGA).
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- Known hypersensitivity to metformin.
- Pregnant or breast feeding.
- Current or lifetime diagnosis of anorexia nervosa or bulimia nervosa.
- Significant risk for dangerousness to self or to others that makes participating inadvisable.
- Language issues that prevent child and/or parent from completing assessments or treatment.
- Ongoing or previously undisclosed child abuse requiring new department of social service intervention.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina, Department of Psychiatry
Chapel Hill, North Carolina, 27599
About this study
The purpose of this study is to evaluate the relative risks and benefits of two approaches to the control of weight gain and other negative side effects in children and adolescents on 2nd generation antipsychotics (SGA):
- Healthy lifestyle instruction (nutritional and physical activity surveillance and advice) + continuation of current SGA;
- Add the diabetes drug, metformin + continuation of current SGA.
Read the detailed description
The proposed pilot study is being conducted to obtain pilot data to support a grant application for a multi-site randomized controlled trial. The primary objective is to evaluate the relative risks and benefits of two approaches to the control of weight gain and other negative side effects in children and adolescents on 2nd generation antipsychotics (SGA). The critical question being addressed is: What can be done for the many youth who have gained substantial weight or developed high levels of lipids or glucose in their blood on an SGA; but due to their illness require continued treatment with an antipsychotic?
At least 40 youths (and no more than 60) age 10-17 that have gained substantial weight while taking a frequently used SGA: ziprasidone, aripiprazole or clozapine will be randomized to one of two treatments for 6 months:
- Healthy lifestyle instruction (nutritional and physical activity surveillance and advice) + continuation of current SGA;
- Add the diabetes drug, metformin + continuation of current SGA.
- Subjects may also elect to be in an observational arm that involves no intervention but the same major assessments.
Height, weight, body fat, and various blood tests indicative of general health will be collected during the 6 month trial to monitor the health benefits and safety of the interventions.
SGAs are associated with concerning degrees of weight gain and metabolic consequences. Children and adolescents, in whom SGAs are used increasingly for a wide variety of conditions, are particularly vulnerable to these side effects, which adversely affect health and longevity. It is imperative that researchers evaluate the efficacy and safety of interventions designed to prevent and treat the weight gain and metabolic problems caused by antipsychotic treatment of children. Lifestyle interventions and adjunctive medications all hold some promise of efficacy. However, it is essential that these strategies be rigorously evaluated as soon as possible in order to prevent the ongoing health consequences of SGA treatment in another generation of children with serious psychiatric illnesses.
- Conditions
- Weight Gain
- Being tested
- metformin, healthy lifestyle intervention
- Keywords
- antipsychotic, metformin, children, adolescents
- Medical subject headings
- Weight Gain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metforminDrug
Also called Glucophage
open dosed, randomly assigned flexible dose treatment with 250-2000mg/day divided BID or TID
healthy lifestyle interventionBehavioural
additional component to regular psychiatric visits that includes monitoring of lifestyle and eating behaviors.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | metformin, 250mg-2000 mg/day, in BID to TID doses for 26 weeks. Open, flexibly adjusted. Receives: Drug: metformin |
| 2 | Experimental | Healthy lifestyle intervention. Additional meeting at each psychiatric visit to review weight changes, level of physical activity and healthy eating behaviors Receives: Behavioral: healthy lifestyle intervention |
| 3 | No intervention | Self-selected patients will be followed at major timepoints to assess weight and related measures. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in BMI
Measured: 24 weeks
Absolute Change in Weight
Measured: 24 weeks
Percent Change in Fat Mass
Measured: 24 weeks
Percent Change in Weight
Measured: 24 weeks
Secondary outcomes (7)
Percent Change in Insulin Levels
Measured: 24 weeks
Percent Change in Total Cholesterol
Measured: 24 weeks
Percent Change in Triglycerides
Measured: 24 weeks
Incidence of Metabolic Syndrome
Measured: 24 weeks
Percent Change in Glucose Levels
Measured: 24 weeks
Percent Change in HDL
Measured: 24 weeks
Percent Change in LDL
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2008 (estimated)
- Study startMar 2007
- Primary completionJun 2010
- Study completionSep 2010
Why it stopped: Terminated in lieu of similar,competing large, multi-site study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Weight GainStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation of Hope, North Carolina
- Responsible party
- Principal investigator, Linmarie Sikich, MD, University of North Carolina, Chapel Hill
- Investigators
- Linmarie Sikich, MD, Principal investigator, University of North Carolina, Department of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00617058
- Sponsor's protocol ID
- 05-3110 GCRC-2529
- Acronym
- ZAC
- Status last verified
- Nov 2012
- First submitted
- 5 Feb 2008
- Last updated
- 31 Dec 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Metabolic Parameters of Antipsychotic Child Treatment With Ziprasidone, Aripiprazole, and Clozapine
- ClinicalTrials.gov ID
- NCT00617058
- Acronym / sponsor ID
- ZAC / 05-3110 GCRC-2529
- Conditions
- Weight Gain
- Keywords
- antipsychotic, metformin, children, adolescents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated in lieu of similar,competing large, multi-site study.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Foundation of Hope, North Carolina
- Study start
- Mar 2007
- Primary completion
- Jun 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 15 Feb 2008 (estimated)
- Results
- Posted 31 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the relative risks and benefits of two approaches to the control of weight gain and other negative side effects in children and adolescents on 2nd generation antipsychotics (SGA):
- Healthy lifestyle instruction (nutritional and physical activity surveillance and advice) + continuation of current SGA;
- Add the diabetes drug, metformin + continuation of current SGA.
Detailed description
The proposed pilot study is being conducted to obtain pilot data to support a grant application for a multi-site randomized controlled trial. The primary objective is to evaluate the relative risks and benefits of two approaches to the control of weight gain and other negative side effects in children and adolescents on 2nd generation antipsychotics (SGA). The critical question being addressed is: What can be done for the many youth who have gained substantial weight or developed high levels of lipids or glucose in their blood on an SGA; but due to their illness require continued treatment with an antipsychotic?
At least 40 youths (and no more than 60) age 10-17 that have gained substantial weight while taking a frequently used SGA: ziprasidone, aripiprazole or clozapine will be randomized to one of two treatments for 6 months:
- Healthy lifestyle instruction (nutritional and physical activity surveillance and advice) + continuation of current SGA;
- Add the diabetes drug, metformin + continuation of current SGA.
- Subjects may also elect to be in an observational arm that involves no intervention but the same major assessments.
Height, weight, body fat, and various blood tests indicative of general health will be collected during the 6 month trial to monitor the health benefits and safety of the interventions.
SGAs are associated with concerning degrees of weight gain and metabolic consequences. Children and adolescents, in whom SGAs are used increasingly for a wide variety of conditions, are particularly vulnerable to these side effects, which adversely affect health and longevity. It is imperative that researchers evaluate the efficacy and safety of interventions designed to prevent and treat the weight gain and metabolic problems caused by antipsychotic treatment of children. Lifestyle interventions and adjunctive medications all hold some promise of efficacy. However, it is essential that these strategies be rigorously evaluated as soon as possible in order to prevent the ongoing health consequences of SGA treatment in another generation of children with serious psychiatric illnesses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: metforminmetformin, 250mg-2000 mg/day, in BID to TID doses for 26 weeks. Open, flexibly adjusted. |
| 2 | Experimental | Behavioral: healthy lifestyle interventionHealthy lifestyle intervention. Additional meeting at each psychiatric visit to review weight changes, level of physical activity and healthy eating behaviors |
| 3 | No intervention | –Self-selected patients will be followed at major timepoints to assess weight and related measures. |
Who may qualify
- Ages
- 10 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Ages 10 to 17 years (inclusive).
- Receiving treatment with ziprasidone, aripiprazole or clozapine for the past 56 days or longer.
- Clinically stable on current treatment regimen (see Rationales below).
- Stable dose of current psychotropic co-medications for at least 30 days.
- BMI increase of > 7% within 3 months OR a > 0.5 BMI z-score increase within the past 24 months while taking olanzapine, quetiapine or risperidone, with maintenance of the threshold level of weight gain.
Key exclusion criteria (12 listed)
- Any medication that would significantly alter glucose, insulin or lipid levels. Prohibited medications will include, but are not limited to: insulin, steroids, topiramate, sibutramine, orlistat, metformin, amantadine, vitamin E (other than in standard multivitamins), antidiabetic drugs, HIV drugs.
- Major neurological disorder or medical illness that affects weight gain (e.g., unstable thyroid disease), requires a prohibited systemic medication or procedure (e.g., diabetes mellitus [insulin], chronic renal failure [steroids]) or that would prevent participation in physical activity in the healthy lifestyle program.
- Current active thyroid (TSH >18 microIU/ml), 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.
- Fasting glucose > 125 mg/dL on two occasions indicating need for prompt treatment for diabetes.
- Child meets DSM-IV criteria for substance abuse or dependence disorder within the past month, not including tobacco abuse or dependence • Current treatment with more than one antipsychotic medication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| metforminAlso: Glucophageopen dosed, randomly assigned flexible dose treatment with 250-2000mg/day divided BID or TID | Drug | 1 |
| healthy lifestyle interventionadditional component to regular psychiatric visits that includes monitoring of lifestyle and eating behaviors. | Behavioural | 2 |
Primary outcome
Percent Change in BMI
Time frame: 24 weeks
Absolute Change in Weight
Time frame: 24 weeks
Percent Change in Fat Mass
Time frame: 24 weeks
Percent Change in Weight
Time frame: 24 weeks
7 secondary outcomes
Percent Change in Insulin Levels
Time frame: 24 weeks
Percent Change in Total Cholesterol
Time frame: 24 weeks
Percent Change in Triglycerides
Time frame: 24 weeks
Incidence of Metabolic Syndrome
Time frame: 24 weeks
Percent Change in Glucose Levels
Time frame: 24 weeks
Percent Change in HDL
Time frame: 24 weeks
Percent Change in LDL
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Linmarie Sikich, MD principal investigator
University of North Carolina, Department of Psychiatry
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing metformin and healthy lifestyle intervention in people with Weight Gain, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in BMI (time frame: 24 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2012.