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

NCT02544321 | Completed Phase 2 Results

• 2 other identifiers: 15-1309UL1TR001082
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (12)

• Mean Glycemic Variability

  4 weeks

• Hypoglycemia Awareness

  4 weeks

• Augmentation Index

  4 weeks

• Heart Rate Variability (Adults)

  4 weeks

• Heart Rate Variability (Adolescents)

  4 weeks

Study Arms (2)

Bromocriptine QR

ACTIVE COMPARATOR

4 weeks of investigational drug Bromocriptine QR

Drug: Bromocriptine

Placebo

PLACEBO COMPARATOR

4 weeks of placebo

Other: Placebo

Interventions

Bromocriptine DRUG

Also known as: Bromocriptine Quick Release (BCQR)

Bromocriptine QR

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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;
• Tobacco or marijuana use;
• Pregnancy;
• Regular or frequent oral steroid use;
• Current use of insulin sensitizing medications, neuroleptics, ergot-related medications, or triptan medications for migraine,
• Diagnosis or history of psychosis,
• Diabetes of other cause such as Maturity Onset Diabetes of the Young or cystic fibrosis-related diabetes.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

University of Colorado-Denver, Anshutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Tell SS, Schafer M, Vigers T, Baumgartner AD, Lyon E, Gross S, Polsky S, Snell-Bergeon JK, Schauer IE, Nadeau KJ. Bromocriptine quick-release as adjunct therapy in youth and adults with type 1 diabetes: A randomized, placebo-controlled crossover study. Diabetes Obes Metab. 2022 Nov;24(11):2148-2158. doi: 10.1111/dom.14800. Epub 2022 Jul 25.

  PMID: 35712800 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Bromocriptine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ergotamines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Ergolines; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Irene Schauer, MD
• Organization: University of Colorado Denver

clinicalresearchsupportcenter@ucdenver.edu

3037241111

Study Officials

• Irene Schauer, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Kristen Nadeau, MD, MS

  Children's Hospital Colorado/University of Colorado

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2015
• First Posted: September 9, 2015
• Study Start: September 1, 2015
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: September 13, 2021
• Results First Posted: September 13, 2021

Record last verified: 2021-08

Locations

US (1)