Bromocriptine for Patients With Schizophrenia and Impaired Glucose Tolerance
Status:
Recruiting
Trial end date:
2023-08-30
Target enrollment:
Participant gender:
Summary
This is a multicenter open-label, pilot study to evaluate the safety and tolerability of
bromocriptine, a dopamine D2/D3 receptor and serotonin 5-HT2C receptor agonist, as an adjunct
to preexisting standard-of-care antipsychotic drug (APD) regimens in the management of
APD-associated impaired glucose tolerance (IGT)/insulin resistance (IR). The ultimate aim of
the study team is to evaluate the efficacy of bromocriptine in treating the metabolic
disturbances associated with APDs and the hypothesis is that bromocriptine will be a
well-tolerated, safe, and inexpensive way to ameliorate these metabolic complications and
prevent or delay the onset of type 2 diabetes (T2D). This study will be a small,
short-duration pilot focusing on safety and tolerability. Twenty psychiatrically stable
APD-treated outpatients, at two sites (VA Pittsburgh and Stanford), aged 18 to 60 years old,
with schizophrenia and comorbid IGT will be recruited and receive 6 weeks of bromocriptine
(flexibly titrated, 2.5-5.0 mg PO daily). Key inclusion criteria are: 1) currently being
treated with second generation APDs for 3 or more months with no change in dose in the 1
month prior to enrollment, 2) fasting glucose 100 to 125mg/dL and/or hemoglobin A1c (HbA1c)
5.7-6.4%. Key exclusions are: 1) prior APD nonadherence, 2) drug/alcohol abuse in the 3
months prior to screening, 3) a history of violent behavior/psychoses, 4) pregnancy, or 5) a
diagnosis of diabetes. Subjects on other dopamine agonists or on medications that may
interact with bromocriptine and those taking corticosteroids or other medications that may
alter glucose levels will be excluded. The purposes of the study are to demonstrate
safety/tolerability, demonstrate feasibility, provide proof of concept, and provide an
open-label assessment of the metabolic and psychiatric effects of bromocriptine in patients
with schizophrenia treated with APDs. The primary metabolic outcome measures will be change
in IR as measured by the HOMA-IR and change in IGT measured by HbA1c. Secondary metabolic
outcome measures include body weight, fasting lipids, and prolactin. The specific aims are as
follows: Specific aim 1: To establish the safety and tolerability of bromocriptine in
patients with schizophrenia and IGT/IR treated with APDs. Specific aim 2: To demonstrate
feasibility/proof of concept for an improvement in APD-induced IGT/IR with bromocriptine.