Bromocriptine for Patients With Schizophrenia and Prediabetes

September 16, 2025 updated by: Ronald A. Codario, VA Pittsburgh Healthcare System

Open-label, Flexible-dose Adjunctive Bromocriptine for Patients With Schizophrenia and Prediabetes

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Background: APDs are among the most widely prescribed medications for psychotic, mood, and anxiety disorders including schizophrenia, bipolar disorder, and major depressive disorder. Many APDs, currently available in the United States, particularly second generation APDs, have been associated to varying degrees with significant dysmetabolic side effects including insulin resistance (IR), impaired glucose tolerance (IGT), hypertension, abdominal obesity, and dyslipidemia. Indeed, 32% of patients taking olanzapine develop IR in addition to gaining at least 15% of their baseline bodyweight. These changes substantially increase the risk of developing T2D and cardiovascular disease (CVD). In fact, the prevalence of metabolic dysfunction in APD-treated patients is more than twice that of the general population and leads to poorer long-term outcomes.

Perhaps most concerning is that APD-treated individuals with schizophrenia have a 15-20-year reduction in life expectancy as compared to the general population, with APD-induced IR being a major contributor to this early mortality. Thus, preventing APD-induced metabolic dysfunction may have a significant impact on morbidity and mortality. Currently there is no consistently effective way to prevent APD-associated metabolic dysfunction and reduce the risk of T2D.

Most studies attempting to elucidate the underlying cause of APD-induced metabolic dysfunction have focused on regions of the central nervous system (CNS) associated with metabolic control (i.e. hypothalamus) because these drugs are utilized primarily to treat neuropsychiatric symptoms in the CNS. Consequently, numerous neurotransmitter and neuropeptide systems in the brain, including dopamine and serotonin, have been implicated in the development of APD-induced metabolic side effects.

Rationale: Bromocriptine is a dopamine D2/D3 receptor and serotonin 5-HT2C receptor agonist that the study team proposes as a potential treatment for APD-induced IR. It has received FDA approval for treatment of T2D, having been shown to significantly lower postprandial plasma glucose and hemoglobin A1c (HbA1c) without increasing insulin or C-peptide levels. To date, there are few studies using bromocriptine in schizophrenia. Although most of the studies have been small, the cumulative results have consistently shown safety and benefit in psychiatric patients. Bromocriptine, even when used at high doses, has been found to be safe in APD-treated patients despite theoretical concerns of exacerbating psychosis due to dopaminergic receptor agonism.

Design: This study is a multicenter open-label, dose-escalation pilot to evaluate the safety and tolerability of bromocriptine 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). A total of fifteen APD-treated participants aged 18 to 60 years old with schizophrenia who have been psychiatrically stable for at least 3 months and show signs of IR (obesity [BMI > 30 kg/m2] plus impaired fasting glucose (100-125mg/dL) and/or impaired glucose tolerance (A1c 5.7-6.4%) will receive bromocriptine in an open-label, flexible-dose design. The initial dose will be 2.5mg which will be increased to the 5mg target dose by week one unless limited by side effects. Bromocriptine will be given as adjunctive treatment to a participant's current APD regimen. The ultimate aim of the study team is to evaluate the efficacy of bromocriptine in treating the metabolic disturbances associated with APDs and the overarching 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) in these at-risk patients. That said, this study will be a small, short-duration pilot focusing on safety and tolerability.

The main 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. Psychiatric symptoms will be measured by the Columbia-Suicide Severity Rating Scale (C-SSRS), Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI). General side effects of bromocriptine will be assessed by the UKU Side Effects Scale. The extrapyramidal side effects of APDs will be monitored via the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale (AIMS).

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15240
        • VA Pittsburgh Healthcare System
        • Contact:
        • Principal Investigator:
          • Ronald Codario, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adult males and females, 18-65 years of age, diagnosed with schizophrenia
  2. 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.
  3. 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.
  4. Either fasting glucose of 100 to 125 mg/dL inclusive and/or an A1C in the range between 5.7-6.4%
  5. Body mass index at least 30 kg/m2 at screening visit.
  6. 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
  7. Subject's primary mental health provider concurs that study enrollment is acceptable

Exclusion Criteria:

  1. History of documented APD non-adherence in prior 3 months.
  2. Historical or current diagnosis of diabetes mellitus (type 1, type 2, or other)
  3. Pregnant or breast feeding. Women of child-bearing potential must be surgically-sterile or using reliable methods of birth control.
  4. May not have used oral or parenteral systemic corticosteroids within 3 months prior to study enrollment or have expected use during the course of the study. The use of either inhaled or topical corticosteroids are not exclusion criteria.
  5. 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.
  6. 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.
  7. 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.
  8. May not be taking or have any sensitivity to any other ergot alkaloids (e.g., dihydroergotamine, ergotamine)
  9. PANSS score >90, which is equivalent to "moderately ill"
  10. Any current hepatic or renal disease
  11. Any documented history of violent behavior
  12. Diagnosis of Alcohol use disorder or substance use disorder in the past 12 months unless meeting remission criteria as defined by MINI.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bromocriptine
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
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.
Other Names:
  • bromocriptine pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HOMA-IR
Time Frame: Measured at weeks 0, 4, 6 and 10 (week 10 is four weeks after study drug discontinuation)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Columbia-Suicide Severity Rating Scale (C-SSRS)
Time Frame: Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)
Assesses risk of suicide
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)
Time Frame: Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)
Assesses symptoms of schizophrenia
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
Time Frame: Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)
Assesses general symptoms of psychiatric illness
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
Time Frame: Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)
Broad and general side effect assessment
Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)
Simpson-Angus Scale
Time Frame: Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)
Assesses extrapyramidal side effects
Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)
Abnormal Involuntary Movement Scale (AIMS)
Time Frame: Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)
Assesses extrapyramidal side effects
Measured at weeks 0, 1, 2, 4, 6, 8, and 10 (weeks 8 and 10 are two and four weeks after study drug discontinuation)
Weight
Time Frame: Measured at weeks 0, 1, 2, 4, 6 and 10
in kilograms
Measured at weeks 0, 1, 2, 4, 6 and 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Pittsburgh Healthcare System

Investigators

  • Principal Investigator: Ronald Codario, M.D., VA Pittsburgh Healthcare System

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2026

Primary Completion (Estimated)

July 31, 2026

Study Completion (Estimated)

July 31, 2026

Study Registration Dates

First Submitted

June 15, 2018

First Submitted That Met QC Criteria

June 28, 2018

First Posted (Actual)

July 2, 2018

Study Record Updates

Last Update Posted (Estimated)

September 22, 2025

Last Update Submitted That Met QC Criteria

September 16, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO0002368

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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