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Bromocriptine for Patients With Schizophrenia and Impaired Glucose Tolerance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03575000
Recruitment Status : Recruiting
First Posted : July 2, 2018
Last Update Posted : May 15, 2020
Sponsor:
Collaborator:
Stanford University
Information provided by (Responsible Party):
Ronald A. Codario, VA Pittsburgh Healthcare System

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. 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.

Condition or disease Intervention/treatment Phase
Schizophrenia Glucose Intolerance Drug: Bromocriptine Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label, Flexible-dose Adjunctive Bromocriptine for Patients With Schizophrenia and Impaired Glucose Tolerance
Actual Study Start Date : April 26, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : August 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

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 Name: bromocriptine pill




Primary Outcome Measures :
  1. HOMA-IR [ Time Frame: Measured at weeks 0, 4, 6, 8, and 10 (weeks 8 and 10 are two and 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.


Secondary Outcome Measures :
  1. Weight [ Time Frame: Measured at weeks 0, 1, 2, 4, 6, 8, and 10 ]
    in kilograms

  2. Hemoglobin A1c [ Time Frame: Measured weeks 0 and 6 ]
    Represents a 3 month average of blood glucose

  3. 75g Oral Glucose Tolerance Test [ Time Frame: Measured at weeks 0 and 6 ]
    75g oral glucose solution followed by glucose measurements ate 0, 30, 60, 90, and 120 minutes

  4. 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

  5. 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

  6. 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

  7. Brief Psychiatric Rating Scale (BPRS) [ 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

  8. Pittsburgh Sleep Quality Index (PSQI) [ 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 sleep quality

  9. 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

  10. 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

  11. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Negative urine drug screen at screening visit and baseline (week 0) visit
  7. 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
  8. Subject's primary mental health provider concurs that study enrollment is acceptable
  9. Screening ECG QTc check must be <500ms
  10. PANSS score </=90, which is equivalent to "moderately ill"

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. QTc of >500ms on screening ECG
  12. Any documented history of violent behavior

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03575000


Contacts
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Contact: Crystal Spotts, M.Ed. 412-360-2845 Crystal.Spotts@va.gov

Locations
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United States, Pennsylvania
VA Pittsburgh Healthcare System Recruiting
Pittsburgh, Pennsylvania, United States, 15240
Contact: Crystal Spotts, M.Ed.    412-360-2845    Crystal.Spotts@va.gov   
Contact: Ronald Codario, MD       Ronald.Codario@va.gov   
Principal Investigator: Ronald Codario, MD         
Sponsors and Collaborators
VA Pittsburgh Healthcare System
Stanford University
Investigators
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Principal Investigator: Ronald Codario, M.D. VA Pittsburgh Healthcare System
Publications:

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Responsible Party: Ronald A. Codario, Physician, VA Pittsburgh Healthcare System
ClinicalTrials.gov Identifier: NCT03575000    
Other Study ID Numbers: PRO0002368
First Posted: July 2, 2018    Key Record Dates
Last Update Posted: May 15, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glucose Intolerance
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Bromocriptine
Antiparkinson Agents
Anti-Dyskinesia Agents
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action