MEtformin and Lorcaserin for WeighT Loss in Schizophrenia
Condition: Schizophrenia; Schizoaffective Disorder; Overweight
MeSH terms: Overweight; Weight Loss; Schizophrenia; Psychotic Disorders
Intervention: Lorcaserin; Metformin; Placebo
Intervention description: Max dose of 10 mg BID; Max dose of 1,000 mg BID; Matching placebos will be administered for each drug.
Intervention MeSH terms: Metformin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 71.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: schizophrenia; schizoaffective disorder; overweight; obesity; weight loss; metformin; lorcaserin

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).
    

Eligibility 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.