Type 1 DiabetesPhase 2NCT02544321

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

A Phase 2 study testing Bromocriptine in people with Type 1 Diabetes, run by University of Colorado, Denver at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 12 to 60 years
Conditions the study is for: Type 1 Diabetes
What is being tested?: Bromocriptine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 108 participants
Where: 1 siteUnited States
Study dates: Sep 2015to Jun 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 to 60 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Colorado-Denver, Anshutz Medical Campus
Aurora, Colorado, 80045

Other trials in United States

About this study

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

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
Being tested: Bromocriptine, Placebo
Medical subject headings: Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BromocriptineDrug
Also called Bromocriptine Quick Release (BCQR)
PlaceboOther

Study groups in NCT02544321
Study group	Role	What they receive
Bromocriptine QR	Active comparator	4 weeks of investigational drug Bromocriptine QR Receives: Drug: Bromocriptine
Placebo	Placebo comparator	4 weeks of placebo Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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)
Measured: 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).
Measured: 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.
Measured: 4 weeks

Secondary outcomes (12)

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.
Measured: 4 weeks
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.
Measured: 4 weeks
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).
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2015Jun 2019

First posted9 Sep 2015 (estimated)
Study startSep 2015
Primary completionJun 2019
Study completionJun 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
More trials run by University of Colorado, DenverThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 108 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02544321
Sponsor's protocol ID: 15-1309
Other IDs: UL1TR001082
Status last verified: Aug 2021
First submitted: 26 Aug 2015
Last updated: 13 Sep 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 35712800

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 13 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Bromocriptine Quick Release (QR) as Adjunct Therapy in Type 1 Diabetes
ClinicalTrials.gov ID: NCT02544321
Acronym / sponsor ID: 15-1309
Conditions: Type 1 Diabetes
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 108 participants (actual)
Lead sponsor: University of Colorado, DenverUniversity, hospital or other
Collaborators: Juvenile Diabetes Research Foundation
Study start: Sep 2015
Primary completion: Jun 2019 (actual)
Study completion: Jun 2019 (actual)
First posted: 9 Sep 2015 (estimated)
Results: Posted 13 Sep 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Bromocriptine QR	Active comparator	Drug: Bromocriptine4 weeks of investigational drug Bromocriptine QR
Placebo	Placebo comparator	Other: Placebo4 weeks of placebo

Who may qualify

Ages: 12 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (7 listed)

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,

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BromocriptineAlso: Bromocriptine Quick Release (BCQR)	Drug	Bromocriptine QR
Placebo	Other	Placebo

Primary outcome

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
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)
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).
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.

12 secondary outcomes

Mean Glycemic Variability
Time frame: 4 weeks
Hypoglycemia Awareness
Time frame: 4 weeks
Augmentation Index
Time frame: 4 weeks
Heart Rate Variability (Adults)
Time frame: 4 weeks
Heart Rate Variability (Adolescents)
Time frame: 4 weeks
Sleep Duration
Time frame: 4 weeks
Sleep Quality
Time frame: 4 weeks
Metabolic Markers-glucose and Triglycerides
Time frame: 4 weeks
Metabolic Markers-fatty Acids
Time frame: 4 weeks
Metabolic Markers-glucagon
Time frame: 4 weeks
Metabolic Markers - GLP1
Time frame: 4 weeks
Metabolic Markers - Insulin
Time frame: 4 weeks

Results and safety

Results posted to the registry on 13 Sep 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Bromocriptine QR, Then Placebo	43	41
Placebo, Then Bromocriptine QR	43	39

Primary outcome: Mean Glucose

Time frame: 4 weeks. Least squares mean (Standard Error). Unit: mg/dl

Measure	Bromocriptine QR (Adolescents) n = 40	Bromocriptine QR (Adults) n = 40	Placebo (Adolescents) n = 40	Placebo (Adults) n = 40
Value	182 (5)	165 (5)	181 (5)	165 (5)

Population analysed: Data reflects average glucose levels.

Primary outcome: Insulin Dosing

Time frame: 4 weeks. Least squares mean (Standard Error). Unit: units//kg/day

Measure	Bromocriptine QR (Adolescents) n = 40	Bromocriptine QR (Adults) n = 40	Placebo (Adolescents) n = 40	Placebo (Adults) n = 40
Value	0.9 (.03)	0.54 (.02)	0.88 (.03)	0.56 (0.02)

Primary outcome: Brachial Artery Distensibility

Time frame: 4 weeks. Least squares mean (Standard Error). Unit: %/mmHg

Measure	Bromocriptine QR (Adolescents) n = 40	Bromocriptine QR (Adults) n = 40	Placebo (Adolescents) n = 40	Placebo (Adults) n = 40
Value	6.35 (0.19)	6.2 (0.2)	6.14 (0.19)	6.4 (0.2)

Population analysed: Compared for placebo versus BCQR after 4 weeks of treatment.

Primary outcome: Hyperemia Peripheral Arterial Tonometry (RH-PAT): Reactive Hyperemia Index (RHI)

Time frame: 4 weeks. Least squares mean (Standard Error). Unit: score on a scale

Measure	Bromocriptine QR (Adolescents) n = 40	Bromocriptine QR (Adults) n = 40	Placebo (Adolescents) n = 40	Placebo (Adults) n = 40
Value	1.95 (0.09)	2.1 (0.1)	2.24 (0.09)	2.2 (0.1)

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 months. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Bromocriptine QR (Adolescents)	1 of 42 (2.4%)	13 of 42 (31%)	1 of 42
Bromocriptine QR (Adults)	1 of 42 (2.4%)	17 of 42 (40.5%)	1 of 42
Placebo (Adolescents)	0 of 42 (0%)	1 of 42 (2.4%)	0 of 42
Placebo (Adults)	0 of 42 (0%)	3 of 42 (7.1%)	0 of 42

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35712800Tell 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Irene Schauer, MD, PhD principal investigator

University of Colorado, Denver

Kristen Nadeau, MD, MS principal investigator

Children's Hospital Colorado/University of Colorado

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bromocriptine in people with Type 1 Diabetes, run by University of Colorado, Denver at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Glucose (time frame: 4 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02544321, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2021.