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

Type 1 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02544321
• Other study ID #: 15-1309
• Secondary ID: UL1TR001082
• Status: Completed
• Phase: Phase 2
• Start date: September 2015
• Est. completion date: June 2019

Study information

• Verified date: August 2021
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: June 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• Bromocriptine

Other:
• Placebo

Locations

Country	Name	City	State
United States	University of Colorado-Denver, Anshutz Medical Campus	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Glucose	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	4 weeks
Primary	Insulin Dosing	At the end of each 4 week intervention period, we will measure the effect of BCQR on insulin dosing (units//kg/day)	4 weeks
Primary	Brachial Artery Distensibility	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 weeks
Primary	Hyperemia Peripheral Arterial Tonometry (RH-PAT): Reactive Hyperemia Index (RHI)	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.	4 weeks
Secondary	Mean Glycemic Variability	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.	4 weeks
Secondary	Hypoglycemia Awareness	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.	4 weeks
Secondary	Augmentation Index	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 weeks
Secondary	Heart Rate Variability (Adults)	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.	4 weeks
Secondary	Heart Rate Variability (Adolescents)	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.	4 weeks
Secondary	Sleep Duration	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.	4 weeks
Secondary	Sleep Quality	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.	4 weeks
Secondary	Metabolic Markers-glucose and Triglycerides	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.	4 weeks
Secondary	Metabolic Markers-fatty Acids	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.	4 weeks
Secondary	Metabolic Markers-glucagon	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.	4 weeks
Secondary	Metabolic Markers - GLP1	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.	4 weeks
Secondary	Metabolic Markers - Insulin	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.	4 weeks