ObesityNCT01300637
Effects of Adjunctive Metformin on Metabolic Profiles in Clozapine-treated Schizophrenic Patients
A study testing Metformin in people with Obesity and Metabolic Syndrome, run by Taipei Medical University WanFang Hospital at 1 site in Taiwan.
Trial summary
Background: Several studies have suggested that clozapine has the greatest propensity of all available atypical antipsychotics to induce weight gain and metabolic dysregulation. So it is necessary to conduct some interventions to prevent or treat metabolic dysregulation induced by clozapine. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Obesity, Metabolic Syndrome, Schizophrenia
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteTaiwan
- Study dates
- Nov 2008to Jul 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- phase 1
- fulfilled DSM-IV criteria of schizophrenia or schizoaffective disorder
- 18-65 year of age
- receiving clozapine for at least 6 months.
- phase 2 are those in phase 1 and met the following
- overweight and obese (BMI ≧ 24)
Show all 15Show fewer
- one or more metabolic dysregulation, such as abdominal obesity (waist circumference > 90 cm, in men and > 80 cm, in women
- fasting hypertriglyceridemia, (≥ 150 mg/dL)
- low fasting HDL levels (< 40 mg/dL in men and < 50 mg/dL in women)
- high blood pressure (≥ 130/ ≥ 85 mm Hg or current treatment with antihypertensive medication).
- The exclusion criteria are the following:
- current use of hypoglycemic or hypolipidemic agents
- FPG levels ≥ 126 mg/dL
- women who are pregnant
- known allergy or contraindicated to metformin (including Creatine>1.4 ng/dl abnormal liver function test; chronic cardiopulmonary insufficiency).
Who cannot join
- phase 2
- current use of hypoglycemic or hypolipidemic agents
- FPG levels ≥ 126 mg/dL
- women who are pregnant
- known allergy or contraindicated to metformin (including Creatine>1.4 ng/dl abnormal liver function test
- chronic cardiopulmonary insufficiency).
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Taipei Medical University-WanFang Hospital
Taipei, 116
Chun-Hsin Chen, MD, 886-2-29307930 ext. 53961, chunhsin57@yahoo.com.tw
Mong-Liang Lu, MD, 886-2-29307930 ext. 53961, mongliang@hotmail.com
About this study
Official title: Prevalence of Metabolic Syndrome and Effects of Adjunctive Metformin on Metabolic Profiles in Clozapine-treated Schizophrenic Patients
Background: Several studies have suggested that clozapine has the greatest propensity of all available atypical antipsychotics to induce weight gain and metabolic dysregulation. So it is necessary to conduct some interventions to prevent or treat metabolic dysregulation induced by clozapine.
Metformin has been reported to achieve weight loss in several groups of patients characterized by insulin resistance. Several studies evaluated the effects of metformin on antipsychotics-induced weight gain and study period lasted from 8 to 16 weeks. Long-term metformin use had more robust effect on metabolic dysregulation and body weight in non-psychiatric field.
Read more
Goals: The study goals are two-fold. The first goal is to estimate the prevalence of metabolic dysregulation among clozapine-treated schizophrenic patients in Taiwan. The second goal is to assess the reversal effect of metformin on metabolic disturbance among clozapine-treated schizophrenic patients in a 24-week double-blind, placebo-control trial. The investigators will use metformin 1500 mg/d or placebo in the second phase trial.
Methods: This study will be divided into two phases. The first phase is to estimate the prevalence of metabolic disturbances among clozapine-treated patients. The second will be a randomized, double-blind, and placebo-controlled study of adjunctive metformin for non-DM clozapine-treated patients.
The clozapine dosage was maintained unchanged during the study period. The eligible patients will be randomly assigned to either metformin or identical placebo pills. Metformin will be titrated to 1500 mg/day in 4 weeks. Patients' blood pressure (BP), waist circumference, body weight, fasting plasma glucose (FPG), triglyceride (TG), high-density lipoprotein cholesterol (HDL), insulin, and leptin will be measured at 2, 4, 8, 16, and 24 weeks after the start of metformin.
In a 3-year period, the investigators estimate to recruit 150 clozapine-treated patients in the first phase and 75 fulfill the second phase criteria. The investigators estimate 60 patients complete the second phase intervention (staying in second phase at least 4 weeks).
From this study, the investigators would like to know the prevalence of metabolic dysregulation among clozapine-treated schizophrenic patients and to know the effect of metformin on metabolic profile among non-DM clozapine treated patients.
Read the detailed description
Background: Several studies have suggested that clozapine has the greatest propensity of all available atypical antipsychotics to induce weight gain and metabolic dysregulation. So it is necessary to conduct some interventions to prevent or treat metabolic dysregulation induced by clozapine.
Metformin has been reported to achieve weight loss in several groups of patients characterized by insulin resistance. Several studies evaluated the effects of metformin on antipsychotics-induced weight gain and study period lasted from 8 to 16 weeks. Long-term metformin use had more robust effect on metabolic dysregulation and body weight in non-psychiatric field. In our recent study data showed that after 8 weeks treatment with metformin 1500 mg/day in 24 olanzapine-treated patients, the body weight, fasting levels of glucose, triglyceride, and insulin significantly decreased. Insulin secretion and insulin resistance also decreased significantly. Half of subjects with metabolic syndrome obtained improvement after metformin trial.
Goals: The study goals are two-fold. The first goal is to estimate the prevalence of metabolic dysregulation among clozapine-treated schizophrenic patients in Taiwan. The second goal is to assess the reversal effect of metformin on metabolic disturbance among clozapine-treated schizophrenic patients in a 24-week double-blind, placebo-control trial. We will use metformin 1500 mg/d or placebo in the second phase trial.
Methods: This study will be divided into two phases. The first phase is to estimate the prevalence of metabolic disturbances among clozapine-treated patients. The second will be a randomized, double-blind, and placebo-controlled study of adjunctive metformin for non-DM clozapine-treated patients.
Patients are recruited in the first phase if they meet the following criteria (1) fulfilled DSM-IV criteria of schizophrenia or schizoaffective disorder; (2) 18-65 year of age (3) receiving clozapine for at least 6 months. We will check patients' blood pressure (BP), waist circumference, body weight, fasting plasma glucose (FPG), triglyceride (TG), high-density lipoprotein cholesterol (HDL), insulin, and leptin will be measured. In this study, we use the modified ATP III criteria for Asians to evaluate subjects for a diagnosis of metabolic syndrome.
The inclusion criteria of second phase intervention will be first-phase participants who are (1) overweight and obese (BMI ≧ 24) or (2) one or more metabolic dysregulation, such as abdominal obesity (waist circumference > 90 cm, in men and > 80 cm, in women; fasting hypertriglyceridemia, (≥ 150 mg/dL); low fasting HDL levels (< 40 mg/dL in men and < 50 mg/dL in women); high blood pressure (≥ 130/ ≥ 85 mm Hg or current treatment with antihypertensive medication). The exclusion criteria are the following: (1) current use of hypoglycemic or hypolipidemic agents (2) FPG levels ≥ 126 mg/dL; (3) women who are pregnant; (4) known allergy or contraindicated to metformin (including Creatine>1.4 ng/dl; abnormal liver function test; chronic cardiopulmonary insufficiency).
The clozapine dosage was maintained unchanged during the study period. The eligible patients will be randomly assigned to either metformin or identical placebo pills. Metformin will be titrated to 1500 mg/day in 4 weeks. Patients' blood pressure (BP), waist circumference, body weight, fasting plasma glucose (FPG), triglyceride (TG), high-density lipoprotein cholesterol (HDL), insulin, and leptin will be measured at 2, 4, 8, 16, and 24 weeks after the start of metformin.
In a 3-year period, we estimate to recruit 150 clozapine-treated patients in the first phase and 75 fulfill the second phase criteria. We estimate 60 patients complete the second phase intervention (staying in second phase at least 4 weeks).
From this study, we would like to know the prevalence of metabolic dysregulation among clozapine-treated schizophrenic patients and to know the effect of metformin on metabolic profile among non-DM clozapine treated patients.
Key words: schizophrenia, clozapine, metabolic dysregulation, metformin
- Conditions
- Obesity, Metabolic Syndrome, Schizophrenia
- Being tested
- Metformin, placebo
- Keywords
- schizophrenia, clozapine, metabolic dysregulation, metformin
- Medical subject headings
- Obesity, Metabolic Syndrome, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Diaformin 500 mg/pill
metformin 500 mg/pill; target dose 1500 mg/day for 24 weeks
placeboDrug
Also called Diaformin 500 mg/pill identical-appearing placebo
identical-appearing pill of placebo
| Study group | Role | What they receive |
|---|---|---|
| metformin | Active comparator | metformin intervention group Receives: Drug: Metformin |
| placebo | Placebo comparator | placebo-controlled Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
body weight change
We measure body weight before and after intervention, at week 2, 4, 8, 16, 24
Measured: 24 weeks
Secondary outcomes (1)
metabolic features
Our secondary outcomes included waist circumference, blood pressure, triglyceride, HDL-C, fasting glucose and insulin.
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 posted21 Feb 2011 (estimated)
- Study startNov 2008
- Primary completionApr 2009 (estimated)
- Study completionJul 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taipei Medical University WanFang Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Science and Technology Council, Taiwan
- Investigators
- Chun-Hsin Chen, MD, Principal investigator, Taipei Medical University-WanFang Hospital, Taipei, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01300637
- Sponsor's protocol ID
- 96064
- Status last verified
- Feb 2011
- First submitted
- 17 Feb 2011
- Last updated
- 21 Feb 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Chen CH, Huang MC, Kao CF, Lin SK, Kuo PH, Chiu CC, Lu ML. Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: a 24-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2013 May;74(5):e424-30. doi: 10.4088/JCP.12m08186.
PubMed 23759461
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevalence of Metabolic Syndrome and Effects of Adjunctive Metformin on Metabolic Profiles in Clozapine-treated Schizophrenic Patients
- ClinicalTrials.gov ID
- NCT01300637
- Acronym / sponsor ID
- 96064
- Conditions
- Obesity, Metabolic Syndrome, Schizophrenia
- Keywords
- schizophrenia, clozapine, metabolic dysregulation, metformin
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Taipei Medical University WanFang HospitalUniversity, hospital or other
- Collaborators
- National Science and Technology Council, Taiwan
- Study start
- Nov 2008
- Primary completion
- Apr 2009 (estimated)
- Study completion
- Jul 2011 (estimated)
- First posted
- 21 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: Several studies have suggested that clozapine has the greatest propensity of all available atypical antipsychotics to induce weight gain and metabolic dysregulation. So it is necessary to conduct some interventions to prevent or treat metabolic dysregulation induced by clozapine.
Metformin has been reported to achieve weight loss in several groups of patients characterized by insulin resistance. Several studies evaluated the effects of metformin on antipsychotics-induced weight gain and study period lasted from 8 to 16 weeks. Long-term metformin use had more robust effect on metabolic dysregulation and body weight in non-psychiatric field.
Goals: The study goals are two-fold. The first goal is to estimate the prevalence of metabolic dysregulation among clozapine-treated schizophrenic patients in Taiwan. The second goal is to assess the reversal effect of metformin on metabolic disturbance among clozapine-treated schizophrenic patients in a 24-week double-blind, placebo-control trial. The investigators will use metformin 1500 mg/d or placebo in the second phase trial.
Methods: This study will be divided into two phases. The first phase is to estimate the prevalence of metabolic disturbances among clozapine-treated patients. The second will be a randomized, double-blind, and placebo-controlled study of adjunctive metformin for non-DM clozapine-treated patients.
The clozapine dosage was maintained unchanged during the study period. The eligible patients will be randomly assigned to either metformin or identical placebo pills. Metformin will be titrated to 1500 mg/day in 4 weeks. Patients' blood pressure (BP), waist circumference, body weight, fasting plasma glucose (FPG), triglyceride (TG), high-density lipoprotein cholesterol (HDL), insulin, and leptin will be measured at 2, 4, 8, 16, and 24 weeks after the start of metformin.
In a 3-year period, the investigators estimate to recruit 150 clozapine-treated patients in the first phase and 75 fulfill the second phase criteria. The investigators estimate 60 patients complete the second phase intervention (staying in second phase at least 4 weeks).
From this study, the investigators would like to know the prevalence of metabolic dysregulation among clozapine-treated schizophrenic patients and to know the effect of metformin on metabolic profile among non-DM clozapine treated patients.
Detailed description
Background: Several studies have suggested that clozapine has the greatest propensity of all available atypical antipsychotics to induce weight gain and metabolic dysregulation. So it is necessary to conduct some interventions to prevent or treat metabolic dysregulation induced by clozapine.
Metformin has been reported to achieve weight loss in several groups of patients characterized by insulin resistance. Several studies evaluated the effects of metformin on antipsychotics-induced weight gain and study period lasted from 8 to 16 weeks. Long-term metformin use had more robust effect on metabolic dysregulation and body weight in non-psychiatric field. In our recent study data showed that after 8 weeks treatment with metformin 1500 mg/day in 24 olanzapine-treated patients, the body weight, fasting levels of glucose, triglyceride, and insulin significantly decreased. Insulin secretion and insulin resistance also decreased significantly. Half of subjects with metabolic syndrome obtained improvement after metformin trial.
Goals: The study goals are two-fold. The first goal is to estimate the prevalence of metabolic dysregulation among clozapine-treated schizophrenic patients in Taiwan. The second goal is to assess the reversal effect of metformin on metabolic disturbance among clozapine-treated schizophrenic patients in a 24-week double-blind, placebo-control trial. We will use metformin 1500 mg/d or placebo in the second phase trial.
Methods: This study will be divided into two phases. The first phase is to estimate the prevalence of metabolic disturbances among clozapine-treated patients. The second will be a randomized, double-blind, and placebo-controlled study of adjunctive metformin for non-DM clozapine-treated patients.
Patients are recruited in the first phase if they meet the following criteria (1) fulfilled DSM-IV criteria of schizophrenia or schizoaffective disorder; (2) 18-65 year of age (3) receiving clozapine for at least 6 months. We will check patients' blood pressure (BP), waist circumference, body weight, fasting plasma glucose (FPG), triglyceride (TG), high-density lipoprotein cholesterol (HDL), insulin, and leptin will be measured. In this study, we use the modified ATP III criteria for Asians to evaluate subjects for a diagnosis of metabolic syndrome.
The inclusion criteria of second phase intervention will be first-phase participants who are (1) overweight and obese (BMI ≧ 24) or (2) one or more metabolic dysregulation, such as abdominal obesity (waist circumference > 90 cm, in men and > 80 cm, in women; fasting hypertriglyceridemia, (≥ 150 mg/dL); low fasting HDL levels (< 40 mg/dL in men and < 50 mg/dL in women); high blood pressure (≥ 130/ ≥ 85 mm Hg or current treatment with antihypertensive medication). The exclusion criteria are the following: (1) current use of hypoglycemic or hypolipidemic agents (2) FPG levels ≥ 126 mg/dL; (3) women who are pregnant; (4) known allergy or contraindicated to metformin (including Creatine>1.4 ng/dl; abnormal liver function test; chronic cardiopulmonary insufficiency).
The clozapine dosage was maintained unchanged during the study period. The eligible patients will be randomly assigned to either metformin or identical placebo pills. Metformin will be titrated to 1500 mg/day in 4 weeks. Patients' blood pressure (BP), waist circumference, body weight, fasting plasma glucose (FPG), triglyceride (TG), high-density lipoprotein cholesterol (HDL), insulin, and leptin will be measured at 2, 4, 8, 16, and 24 weeks after the start of metformin.
In a 3-year period, we estimate to recruit 150 clozapine-treated patients in the first phase and 75 fulfill the second phase criteria. We estimate 60 patients complete the second phase intervention (staying in second phase at least 4 weeks).
From this study, we would like to know the prevalence of metabolic dysregulation among clozapine-treated schizophrenic patients and to know the effect of metformin on metabolic profile among non-DM clozapine treated patients.
Key words: schizophrenia, clozapine, metabolic dysregulation, metformin
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| metformin | Active comparator | Drug: Metforminmetformin intervention group |
| placebo | Placebo comparator | Drug: placeboplacebo-controlled |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- phase 1
- fulfilled DSM-IV criteria of schizophrenia or schizoaffective disorder
- 18-65 year of age
- receiving clozapine for at least 6 months.
- phase 2 are those in phase 1 and met the following
Key exclusion criteria (6 listed)
- phase 2
- current use of hypoglycemic or hypolipidemic agents
- FPG levels ≥ 126 mg/dL
- women who are pregnant
- known allergy or contraindicated to metformin (including Creatine>1.4 ng/dl abnormal liver function test
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: Diaformin 500 mg/pillmetformin 500 mg/pill; target dose 1500 mg/day for 24 weeks | Drug | metformin |
| placeboAlso: Diaformin 500 mg/pill identical-appearing placeboidentical-appearing pill of placebo | Drug | placebo |
Primary outcome
body weight change
Time frame: 24 weeks
We measure body weight before and after intervention, at week 2, 4, 8, 16, 24
1 secondary outcome
metabolic features
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2011.
- Derived from this study: PubMed 23759461Chen CH, Huang MC, Kao CF, Lin SK, Kuo PH, Chiu CC, Lu ML. Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: a 24-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2013 May;74(5):e424-30. doi: 10.4088/JCP.12m08186.
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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.
Chun-Hsin Chen, MD principal investigator
Taipei Medical University-WanFang Hospital, Taipei, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Metformin in people with Obesity and Metabolic Syndrome, run by Taipei Medical University WanFang Hospital at 1 site in Taiwan.
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 15 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 21 Feb 2011. 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 Taiwan. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chun-Hsin Chen, MD (886-2-29307930 ext. 53961, chunhsin57@yahoo.com.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
body weight change (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01300637, which also lists 1 linked publication.
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 21 Feb 2011.