Bromocriptine for Patients With Schizophrenia and Prediabetes

NCT03575000 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: PRO0002368
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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. A total of 15 psychiatrically stable APD-treated adult outpatients, VA Pittsburgh , aged 18 to 65 years old, with a confirmed diagnosis of 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.

Conditions

Schizophrenia; PreDiabetes

Outcome Measures

Primary Outcomes (1)

• HOMA-IR

  The primary metabolic outcome measures will be change in IR as measured by HOMA-IR which is calculated with fasting insulin and glucose.

  Measured at weeks 0, 4, 6 and 10 (week 10 is four weeks after study drug discontinuation)

Secondary Outcomes (7)

• Weight

  Measured at weeks 0, 1, 2, 4, 6 and 10

• Columbia-Suicide Severity Rating Scale (C-SSRS)

  Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)

• Positive and Negative Syndrome Scale (PANSS)

  Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)

• Clinical Global Impression

  Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)

• UKU Side Effects Scale

  Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)

Study Arms (1)

Bromocriptine

EXPERIMENTAL

This is an open-label study, so there is no comparator group. As such there is only one arm. Subjects will receive bromocriptine at a starting dose of 2.5mg daily which will be increased, if tolerated, to 5mg daily after one week. Bromocriptine will be continued for a total of 6 weeks. Laboratory investigations, telephonic interviews, and face to face visits with subjects will be conducted before, during, and after the time period that bromocriptine will be used as detailed in the study design section.

Drug: Bromocriptine

Interventions

Bromocriptine DRUG

This is an open-label study, so there is no comparator group. As such there is only one arm. Subjects will receive bromocriptine at a starting dose of 2.5mg daily which will be increased, if tolerated, to 5mg daily after one week. Bromocriptine will be continued for a total of 6 weeks. Laboratory investigations, telephonic interviews, and face to face visits with subjects will be conducted before, during, and after the time period that bromocriptine will be used as detailed in the study design section.

Also known as: bromocriptine pill

Bromocriptine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males and females, 18-65 years of age, diagnosed with schizophrenia
• Female participants must test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control (e.g., oral contraceptives, birth control diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, intrauterine devices, partner with vasectomy, or abstinence) until the study is complete.
• Be treated with FDA-approved second generation antipsychotic medication for at least 3 months, with no change in dose in the 1 month prior to enrollment.
• Either fasting glucose of 100 to 125 mg/dL inclusive and/or an A1C in the range between 5.7-6.4%
• Body mass index at least 30 kg/m2 at screening visit.
• Subject must be willing to provide contact information for a close family member or friend that will contact the study team if the participant exhibits signs of psychological deterioration
• Subject's primary mental health provider concurs that study enrollment is acceptable

You may not qualify if:

• History of documented APD non-adherence in prior 3 months.
• Historical or current diagnosis of diabetes mellitus (type 1, type 2, or other)
• Pregnant or breast feeding. Women of child-bearing potential must be surgically-sterile or using reliable methods of birth control.
• May not be taking any antidiabetic/antihyperglycemic medications (e.g., metformin, sulfonylureas, thiazolidinediones, insulin, DPP-IV inhibitors, SGLT-2 inhibitors, etc.) currently or within 4 months prior to study enrollment.
• May not be taking any of the following cytochrome P450 3A4 (CYP3A4) inhibitors: protease inhibitors (atazanavir, boceprevir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, telaprevir); certain antibiotics/antifungals (clarithromycin, erythromycin, telithromycin, chloramphenicol, ciprofloxacin, fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole); nefazodone; aprepitant; imatinib; certain calcium channel blockers (diltiazem, verapamil); Valerian; or grapefruit/grapefruit juice.
• May not be taking or have sensitivity to any dopamine agonist medications (e.g., bromocriptine, cabergoline, pramipexole,ropinirole, rotigotine, etc.) currently or within 3 months prior to study enrollment.
• May not be taking or have any sensitivity to any other ergot alkaloids (e.g., dihydroergotamine, ergotamine)
• PANSS score \>90, which is equivalent to "moderately ill"
• Any current hepatic or renal disease
• Any documented history of violent behavior
• Diagnosis of Alcohol use disorder or substance use disorder in the past 12 months unless meeting remission criteria as defined by MINI.

Sponsors & Collaborators

• VA Pittsburgh Healthcare System: lead

Study Sites (1)

VA Pittsburgh Healthcare System

Pittsburgh, Pennsylvania, 15240, United States

Location

Related Publications (16)

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  PMID: 16803851 BACKGROUND

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MeSH Terms

Conditions

Schizophrenia; Prediabetic State

Interventions

Bromocriptine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Ergotamines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Ergolines; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ronald Codario, M.D.

  VA Pittsburgh Healthcare System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mary McShea, MS

CONTACT

412-360-2300; mary.mcshea@va.gov

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: June 15, 2018
• First Posted: July 2, 2018
• Study Start: January 1, 2026
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)