Bromocriptine for Schizophrenia and Diabetes-Related Issues

Overseen By Mary McShea, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Pittsburgh Healthcare System

Must be taking: Second generation antipsychotics

Must not be taking: Corticosteroids, Antidiabetics, CYP3A4 inhibitors, Dopamine agonists

Disqualifiers: Diabetes, Pregnancy, Substance use, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

15 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot be on medications that interact with bromocriptine, such as some antibiotics, antifungals, or dopamine agonists, and you must not be taking any antidiabetic medications or corticosteroids. It's best to discuss your current medications with the study team to see if they are allowed.

What data supports the effectiveness of the drug bromocriptine for schizophrenia and diabetes-related issues?

Bromocriptine has been approved for the treatment of type 2 diabetes, showing a modest reduction in blood sugar levels in clinical trials. However, its effectiveness for schizophrenia is less clear, with preliminary data suggesting it may not be very effective for this condition. ^{1 2 3 4 5}

Is bromocriptine generally safe for humans?

Bromocriptine has been used worldwide for over 20 years to treat various conditions like Parkinson's disease and has been found to be generally safe. However, in studies for type 2 diabetes, common side effects included nausea, and there were higher withdrawal rates due to adverse effects compared to placebo. It has a reassuring cardiovascular safety profile over 1 year of use, but long-term safety data is lacking. ^{1 4 5 6 7}

How does the drug bromocriptine differ from other treatments for schizophrenia and diabetes-related issues?

Bromocriptine is unique because it is a dopamine agonist (a substance that activates dopamine receptors) that has been used for various conditions like Parkinson's disease and type 2 diabetes. Its quick-release formulation may help reset circadian rhythms, which could be beneficial for both diabetes and potentially schizophrenia, although its efficacy in schizophrenia is less established. ^{2 3 4 5 8}

Research Team

Ronald Codario, MD

Principal Investigator

VA Pittsburgh Healthcare System

Eligibility Criteria

This trial is for adults aged 18-65 with schizophrenia and impaired glucose tolerance, who have been on second-generation antipsychotic meds for at least 3 months without dose changes. Participants must not be pregnant, have a BMI of at least 30 kg/m2, and no history of diabetes or violent behavior. They should agree to use birth control and provide emergency contact information.

Inclusion Criteria

Subject's primary mental health provider concurs that study enrollment is acceptable

I am not pregnant and agree to use birth control during the study.

My blood sugar or A1C levels are slightly elevated but not diabetic.

Exclusion Criteria

I am not taking any CYP3A4 inhibitor medications.

I am not currently taking, nor have I taken any dopamine agonist medications in the last 3 months.

I have been diagnosed with diabetes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive bromocriptine as an adjunct to their current APD regimen, with doses titrated from 2.5mg to 5mg daily over 6 weeks

6 weeks

Weekly visits (in-person and telephonic)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of psychiatric symptoms and side effects

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Bromocriptine

Trial Overview The study tests the safety and tolerability of bromocriptine as an add-on treatment for patients with schizophrenia taking antipsychotics that may cause blood sugar issues. It aims to see if this drug can prevent or delay type 2 diabetes by improving insulin resistance over a six-week period.

Participant Groups

Group I: Bromocriptine Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

VA Pittsburgh Healthcare System

Lead Sponsor

Trials

36

Recruited

15,900+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

References

1. India pubmed.ncbi.nlm.nih.gov

Bromocriptine, a Dopamine (d2) Receptor Agonist, Used Alone and in Combination with Glipizide in Sub-Therapeutic Doses to Ameliorate Hyperglycaemia. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Bromocriptine and psychosis: a literature review. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Psychiatric applications of bromocriptine therapy. [2013]

4. Malaysia pubmed.ncbi.nlm.nih.gov

Cabergoline effect on blood sugar in type 2 diabetic patients with oral agent failure. [2022]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Quick-release bromocriptine for treatment of type 2 diabetes. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Bromocriptine mesylate for glycemic management in type 2 diabetes mellitus. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Bromocriptine improves glycaemic control and serum lipid profile in obese Type 2 diabetic subjects: a new approach in the treatment of diabetes. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Bromocriptine: old drug, new formulation and new indication. [2022]