MEtformin and Lorcaserin for WeighT Loss in Schizophrenia

• Status: Terminated
• Trial end date: 2020-02-14
• Target enrollment: 0
• Participant gender: All

Summary

Purpose: The purpose of this study is to test new pharmacologic strategies for weight loss in patients with schizophrenia, a population for which no current weight-loss treatments have gained widespread use. The goal is to recruit overweight people with schizophrenia to participate in a 52-week double-blind, randomized study to assess the efficacy and safety of lorcaserin/metformin combination treatment, lorcaserin monotherapy, and placebo on weight, body composition, and measures of glucose and lipid metabolism.

Participants: Approximately 110 subjects will be enrolled at four clinical sites (UNC Chapel Hill, Carolina Behavioral Care, Columbia University, and Augusta University)

Procedures (methods): Behavioral: All participants will be offered a behavioral intervention of weekly diet and exercise counseling aimed at modifying cardiovascular risk factors. This intervention will be provided at all in-person study visits after the Baseline Visit and supplemented with weekly interim phone calls to reinforce lessons between visits. Pharmacological Intervention: All participants who meet entry criteria will be randomized to one of the three treatment groups (lorcaserin/metformin, lorcaserin, and placebo).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Columbia University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Metformin

Criteria

Inclusion Criteria:

• Outpatients with a diagnosis of schizophrenia or schizoaffective disorder as defined by DSM-IV-TR criteria (see Appendix 3 and Appendix 4) and confirmed by the Structured Clinical Interview for DSM-IV (SCID).

• Duration of psychotic illness must be greater than one year, as defined by having initiated antipsychotic treatment at least 1 year prior to study enrollment.

• Must be 18-65 years of age.

• Must demonstrate adequate decisional capacity to make a choice about participating in this research study and must provide written informed consent to participate.

• BMI greater than or equal to 27 kg/m^2

• Currently treated with one or a combination of two FDA-approved antipsychotic medications (typical or atypical antipsychotics) AND on that drug regimen for at least two months prior to study entry (with stable dosages for at least 1 month).

• Concomitant medications are allowed if agents and doses are unchanged for at least 1 month prior to study entry and if these medications are not among those excluded in the Exclusion Criteria.

• Women who can become pregnant must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study in such a manner that the risk of pregnancy is minimized. Acceptable methods include oral, injectable or implanted contraceptives, intrauterine devices or barrier methods such as condoms, diaphragm and spermicides. Women who can become pregnant must have a negative serum pregnancy test at the Screening Visit.

Exclusion Criteria:

• Inpatient status

• Clinical Global Impression Severity (CGI-S) score greater than or equal to 6

• Current treatment with more than 2 antipsychotics

• HbA1c greater than or equal to 6.5%

• Diagnosis of diabetes mellitus or current treatment with insulin or oral hypoglycemics

• Current or prior treatment with metformin within the past 3 months

• Current or prior treatment with lorcaserin within the past 3 months

• Current or prior treatment with a 5-HT2B agonist (e.g. cabergoline) within the past 45 days due to potential risk for heart valve defects

• Current treatment with two or more antidepressants

• Current treatment with a single antidepressant prescribed in excess of the maximum approved dose

• Current treatment with monoamine oxidase inhibitor (MAOI) class of antidepressants (isocarboxazid, phenelzine, selegiline, tranylcypromine)

• Concurrent treatment with any of the following pro-serotonergic drugs: meperidine, buspirone, dextromethorphan, triptans, tramadol, ritonavir, tryptophan, ginseng, St. John's wort

• Diagnosis of congestive heart failure

• Uncorrected thyroid disorder

• Renal impairment as evidenced by estimated glomerular filtration rate (eGFR) 50 mL/min/1.73 m^2

• Hepatic disease (ALT, AST, or GGT > 2 times upper limit of normal (ULN), total bilirubin > 1.2 times ULN)

• Metabolic acidosis (serum CO2 <20 mEq/L)

• Known hypersensitivity to metformin or lorcaserin

• Women who are pregnant or breastfeeding

• Recent (in the past 30 days) or scheduled radiological studies involving iodinated contrast material

• Alcohol abuse/dependence as determined by SCID within the past month

• Other serious and unstable medical condition in the judgment of the investigator

• DSM-IV diagnosis of mental retardation or dementia

• Any medication (prescription or non-prescription) used for weight loss must have been discontinued 3 months prior to study entry.