Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Bromocriptine Quick Release (BCQR) as Adjunct Therapy in Type 1 Diabetes

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02544321
Recruitment Status : Completed
First Posted : September 9, 2015
Results First Posted : September 13, 2021
Last Update Posted : September 13, 2021
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
Type 1 diabetes (T1D) continues to be a disease plagued by hyperglycemia, insulin resistance (IR), and increased cardiovascular disease (CVD) despite advances in insulin delivery and glucose monitoring. Therefore new approaches are needed. Bromocriptine (BC), a dopamine (DA) agonist, has long been widely used for treating Parkinson's disease and prolactinoma. Its recent approval in a quick release formulation, BCQR, for type 2 diabetes (T2D) is an exciting development, representing a novel mechanism for improving IR. BCQR has not been studied in T1D, but it's mechanism of action, mechanistic studies, and preliminary data support the proposed study of possible benefits of BCQR on insulin action, glycemic control, and the vasculature in T1D. This study has received an exemption from the FDA to study BCQR in adults with T1D and an IND approval (131360) to study BCQR in adolescents with T1D. This is a random-order, double-blind, placebo-controlled study of a 4 week intervention. Outcomes will include fasting and postprandial glucose, glycemic variability, insulin dosing, hypoglycemia frequency and awareness, sleep quality, and metabolic hormone levels.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Drug: Bromocriptine Other: Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Bromocriptine Quick Release (QR) as Adjunct Therapy in Type 1 Diabetes
Study Start Date : September 2015
Actual Primary Completion Date : June 2019
Actual Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Active Comparator: Bromocriptine QR
4 weeks of investigational drug Bromocriptine QR
Drug: Bromocriptine
Other Name: Bromocriptine Quick Release (BCQR)

Placebo Comparator: Placebo
4 weeks of placebo
Other: Placebo



Primary Outcome Measures :
  1. Mean Glucose [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, we will measure the effect of Bromocriptine Quick Release on average glucose levels (mg/dl) by continuous glucose monitoring

  2. Insulin Dosing [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, we will measure the effect of BCQR on insulin dosing (units//kg/day)

  3. Brachial Artery Distensibility [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, we will measure the brachial artery distensibility as a measure of vascular stiffness by Dynapulse (%/mmHg). A larger number indicates less stiffness (ie greater compliance).

  4. Hyperemia Peripheral Arterial Tonometry (RH-PAT): Reactive Hyperemia Index (RHI) [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, we will measure the reactive hyperemia Index (RHI). The Reactive Hyperemia Index (RHI) measures increased bloodflow after vascular occlusion. Higher scores indicate lower CVD risk and a better outcome, Scores of less than 1.67 may be considered abnormal. Scores of 1.67 1.67-2.09 may be considered borderline, and scores of 2.10 or higher my be considered normal.


Secondary Outcome Measures :
  1. Mean Glycemic Variability [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, we will measure the effect of Bromocriptine Quick Release on glycemic variability throughout the day (mg/dl), measured as SD of all glucose values throughout the last 7 days of intervention. Incorrectly initially entered as primary outcome. per protocol this has always been a secondary outcome.

  2. Hypoglycemia Awareness [ Time Frame: 4 weeks ]

    At the end of each 4 week intervention period, we will measure Hypoglycemia Awareness using the Gold method (7 point Likert scale: Possible scores range from 1 to 7. higher scores indicate more impaired awareness of hypoglycemia, and a worse outcome), Clarke method (8 question questionnaire characterizing hypoglycemia awareness. Possible scores range from 0-7, with higher scores indicating less awareness and a worse outcome), and the McAuley score (list of symptoms with a 7 point Likert scale for each. Possible scores range from 1-7 for each item, and are averaged across all symptoms, for a total possible score range of 1-7, with higher scores indicating more symptom awareness, and a better outcome).

    Incorrectly initially entered as primary outcome. per protocol this has always been a secondary outcome.


  3. Augmentation Index [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, the % will be measured by SyphgmoCor. The Augmentation Index measures vascular stiffness by comparing pulse pressure of the reflected wave to the primary wave. HIGHER scores indicate greater vascular stiffness and higher cardiovascular risk, but a normal range has not been clearly defined. Presented as AI normalized to a heart rate of 75 (AI75).

  4. Heart Rate Variability (Adults) [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period we will measure the autonomic function by ECG. Ratio of maximum heart rate/minimum heartrate during a valsalva maneuver.

  5. Heart Rate Variability (Adolescents) [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period we will measure the autonomic function by HRV measured by endopat and reported using the single gold standard measure of SDNN (standard deviation of beat to beat time interval). Normal is >100, 50-100 indicates compromised autonomic function.

  6. Sleep Duration [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, measurements of sleep duration on weekdays and weekends (minutes) by a Philips Spectrum Plus sleep monitor will be obtained.

  7. Sleep Quality [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, measurements of sleep efficiency (percent of time in bed spent asleep) during the week and on weekends by a Philips Spectrum Plus sleep monitor will be obtained.

  8. Metabolic Markers-glucose and Triglycerides [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, glucose, insulin, triglycerides, NEFA, GLP-1, and glucagon area under the curve will be measured during Mixed Meal Tolerance Test.

  9. Metabolic Markers-fatty Acids [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, glucose, insulin, triglycerides, NEFA, GLP-1, and glucagon area under the curve will be measured during Mixed Meal Tolerance Test.

  10. Metabolic Markers-glucagon [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, glucose, insulin, triglycerides, NEFA, GLP-1, and glucagon area under the curve will be measured during Mixed Meal Tolerance Test.

  11. Metabolic Markers - GLP1 [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, glucose, insulin, triglycerides, NEFA, GLP-1, and glucagon area under the curve will be measured during Mixed Meal Tolerance Test.

  12. Metabolic Markers - Insulin [ Time Frame: 4 weeks ]
    At the end of each 4 week intervention period, glucose, insulin, triglycerides, NEFA, GLP-1, and glucagon area under the curve will be measured during Mixed Meal Tolerance Test.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Type 1 Diabetes (T1D) of >1 year duration based on a clinical course consistent with T1D and rapid conversion to insulin requirement after diagnosis.
  2. HbA1c 6.5-10% (adults) or any HbA1c up to 12% (pediatrics)
  3. age 12-60 years of age

Exclusion Criteria:

  1. Any comorbid condition associated with inflammation, insulin resistance, or dyslipidemia including cancer, heart failure, active or end stage liver disease, kidney disease (except microalbuminuria), inadequately treated thyroid disease, or rheumatologic disease;
  2. Tobacco or marijuana use;
  3. Pregnancy;
  4. Regular or frequent oral steroid use;
  5. Current use of insulin sensitizing medications, neuroleptics, ergot-related medications, or triptan medications for migraine,
  6. Diagnosis or history of psychosis,
  7. Diabetes of other cause such as Maturity Onset Diabetes of the Young or cystic fibrosis-related diabetes.

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): NCT02544321


Locations
Layout table for location information
United States, Colorado
University of Colorado-Denver, Anshutz Medical Campus
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Juvenile Diabetes Research Foundation
Investigators
Layout table for investigator information
Principal Investigator: Irene Schauer, MD, PhD University of Colorado, Denver
Principal Investigator: Kristen Nadeau, MD, MS Children's Hospital Colorado/University of Colorado
  Study Documents (Full-Text)

Documents provided by University of Colorado, Denver:
Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02544321    
Other Study ID Numbers: 15-1309
UL1TR001082 ( U.S. NIH Grant/Contract )
First Posted: September 9, 2015    Key Record Dates
Results First Posted: September 13, 2021
Last Update Posted: September 13, 2021
Last Verified: August 2021
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System 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