E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Antipsychotic-induced weight gain (AiWG) |
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E.1.1.1 | Medical condition in easily understood language |
Antipsychotic-induced weight gain |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To optimize the application of an existing drug, metformin, for a new indication, AiWG, by showing that metformin in combination with lifestyle interventions reduces AiWG compared to placebo in combination with lifestyle interventions. |
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E.2.2 | Secondary objectives of the trial |
Furthermore, we aim to investigate the difference in reduction of AiWG between subgroups; clozapine use versus other antipsychotic use and patients with schizophrenia and bipolar disorder. Additionally, we aim to examine the difference in metformin-induced weight reduction between participants on high-risk agents -risperidone, olanzapine, clozapine and quetiapine- vs. all other antipsychotics and between self-reported weight gain due to antipsychotic use vs weight gain due to other reasons. At last, we aim to assess whether metformin compared to placebo improves metabolic traits, quality of life, general physical and psychological health, cost effectiveness and whether genetic liability to BMI and metabolic syndrome may help estimate weight reduction following initiation of metformin treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Have a diagnosis of schizophrenia spectrum disorders according to DSM-IV-TR or DSM-5 criteria as summarized in DSM-5 chapter Schizophrenia Spectrum and other Psychotic Disorders, with the exception of substance/medication-induced psychotic disorder, psychotic disorder due to another medical condition, catatonia associated with another mental disorder, catatonic disorder due to another medical condition, and unspecified catatonia. Thus, included may be participants with a delusional disorder, schizotypal personality disorder, brief psychotic disorder, schizophreniform disorder, schizophrenia, schizoaffective disorder, other specified schizophrenia spectrum and other psychotic disorder, and unspecified schizophrenia and other psychotic disorder; 2. Have a diagnosis of bipolar disorder according to DSM-IV-TR or DSM-5 criteria. 3. Have been using an antipsychotic for at least 3 months (as most AiWG occurs in the first weeks to months of treatment; the participant may have switched antipsychotic use in the past 3 months); 4. Are willing to undergo lifestyletherapy; 5. Speak and read Dutch; 6. Are found mentally competent by their treating physician; 7. Are at least 16 years of age; 8. Are overweight (BMI>25);
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E.4 | Principal exclusion criteria |
1. Suffer from neurodegenerative extrapyramidal disease; 2. Carry metformin-related contra-indications, i.e.: conditions predisposing to tissue hypoxia (such as congestive heart failure, recent myocardial infarction and respiratory failure), metabolic acidosis, precoma diabeticum, kidney failure (GFR<30ml/min) and conditions predisposing to kidney failure (e.g. dehydration, infections and hypovolemic shock), liver failure and disorders in the use of alcohol defined as > 2 reported consumptions daily and a gGT of over 60U/L or a CDT >2.2% (measured in blood using the N-Latex CDT method). 3. Use of one or more of the following medication(s): -NSAIDs -ACE-inhibitors -ARBs (angiotensin receptor blockers) -diuretics -OCT (organic cation transporters) -1 and 2 inhibitors (e.g. cimetidine, dolutegravir, isavuconazol, trimethoprim, vandetanib, crizotinibib, vandetanib, and verapamil) and inductors (e.g. rifampicin); 4. Suffer from vitamin B12 deficiency; 5. Suffer from diabetes mellitus; 6. Are pregnant or breast feed or women of child bearing age using no contraceptives.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is difference in weight (from treatment inception until 26 weeks of treatment) as a continuous trait. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoints of evaluation: Week 0 (Visit 1) Week 13 (Visit 3) Week 26 (Visit 4) Week 52 (Visit 5) |
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E.5.2 | Secondary end point(s) |
We aim to investigate the difference in reduction of AiWG between subgroups; clozapine use versus other antipsychotic use and between patients with schizophrenia and bipolar disorder. Additionally, we aim to examine the difference in metformin-induced weight reduction between participants on high-risk agents -risperidone, olanzapine, clozapine and quetiapine- vs. all other antipsychotics and between self-reported weight gain due to antipsychotic use vs weight gain due to other reasons. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints of evaluation: Week 0 (Visit 1) Week 13 (Visit 3) Week 26 (Visit 4) Week 52 (Visit 5) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |