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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT02544321
• Collaborator: Juvenile Diabetes Research Foundation (Other)
• Enrollment: 108
• Location: 1
• Arms: 2
• Duration (Months): 45
• Patients Per Site Per Month: 2.4

Study Details

Study Description

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

Study Design

• Study Type: Interventional
• 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: Sep 1, 2015
• Actual Primary Completion Date: Jun 1, 2019
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Bromocriptine QR 4 weeks of investigational drug Bromocriptine QR	Drug: Bromocriptine; Other Names: Bromocriptine Quick Release (BCQR)
Placebo Comparator: Placebo 4 weeks of placebo	Other: Placebo

Outcome Measures

Primary Outcome Measures

1. Mean Glucose [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 [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 [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) [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 [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 [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 [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) [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) [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 [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 [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 [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 [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 [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 [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado-Denver, Anshutz Medical Campus	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver
• Juvenile Diabetes Research Foundation

Investigators

• 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)

• Study Protocol and Statistical Analysis Plan - Nov 29, 2018

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02544321
• Other Study ID Numbers: 15-1309; UL1TR001082
• First Posted: Sep 9, 2015
• Last Update Posted: Sep 13, 2021
• Last Verified: Aug 1, 2021

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Bromocriptine

Study Results

Participant Flow

Pre-assignment Detail	Some participants screen failed or withdrew from the study after enrollment, but prior to starting the study.

Arm/Group Title	Bromocriptine QR, Then Placebo	Placebo, Then Bromocriptine QR
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR, then 4 weeks of placebo.	4 weeks of placebo, then 4 weeks of investigational drug Bromocriptine QR
Period Title: Overall Study
STARTED	43	43
Completed First Treatment	43	41
Completed Washout	43	41
Started Second Treatment	42	40
COMPLETED	41	39
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Bromocriptine QR, Then Placebo	Placebo, Then Bromocriptine QR	Total
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR, then 4 weeks of placebo.	4 weeks of placebo, then 4 weeks of investigational drug Bromocriptine QR	Total of all reporting groups
Overall Participants	43	41	84
Age (years) [Mean (Standard Deviation) ]
Adults	44.1 (9.0)	38 (10.0)	41.1 (9.9)
Adolescents	16.5 (2.8)	15.6 (2.7)	16.1 (2.8)
Sex: Female, Male (Count of Participants)
Female	12 27.9%	11 26.8%	23 27.4%
Male	9 20.9%	10 24.4%	19 22.6%
Female	15 34.9%	9 22%	24 28.6%
Male	7 16.3%	11 26.8%	18 21.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 2.4%	1 1.2%
Not Hispanic or Latino	21 48.8%	20 48.8%	41 48.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Hispanic or Latino	1 2.3%	2 4.9%	3 3.6%
Not Hispanic or Latino	21 48.8%	18 43.9%	39 46.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	21 48.8%	21 51.2%	42 50%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 2.4%	1 1.2%
White	22 51.2%	19 46.3%	41 48.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	43 100%	41 100%	84 100%

Outcome Measures

1. Primary Outcome

Title	Mean Glucose
Description	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
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Data reflects average glucose levels.

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of placebo Placebo	4 weeks of placebo Placebo
Measure Participants	40	40	40	40
Least Squares Mean (Standard Error) [mg/dl]	182 (5)	165 (5)	181 (5)	165 (5)

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR	4 weeks of placebo Placebo	4 weeks of placebo
Measure Participants	40	40	40	40
Least Squares Mean (Standard Error) [units//kg/day]	0.9 (.03)	0.54 (.02)	0.88 (.03)	0.56 (0.02)

3. Primary Outcome

Title	Brachial Artery Distensibility
Description	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).
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Compared for placebo versus BCQR after 4 weeks of treatment.

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of placebo Placebo	4 weeks of placebo Placebo
Measure Participants	40	40	40	40
Least Squares Mean (Standard Error) [%/mmHg]	6.35 (0.19)	6.2 (0.2)	6.14 (0.19)	6.4 (0.2)

4. Primary Outcome

Title	Hyperemia Peripheral Arterial Tonometry (RH-PAT): Reactive Hyperemia Index (RHI)
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR	4 weeks of placebo Placebo	4 weeks of placebo
Measure Participants	40	40	40	40
Least Squares Mean (Standard Error) [score on a scale]	1.95 (0.09)	2.1 (0.1)	2.24 (0.09)	2.2 (0.1)

5. Secondary Outcome

Title	Mean Glycemic Variability
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of placebo Placebo	4 weeks of placebo Placebo
Measure Participants	40	40	40	40
Least Squares Mean (Standard Error) [mg/dl]	71 (2.1)	61 (2.5)	73 (2.1)	63 (2.5)

6. Secondary Outcome

Title	Hypoglycemia Awareness
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Unadjusted least square means by mixed procedure.

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR	4 weeks of placebo Placebo	4 weeks of placebo
Measure Participants	40	41	41	41
Gold method scores	2.15 (1.31)	3.02 (1.67)	2.00 (1.18)	3.15 (1.59)
Clarke method scores	1.36 (1.23)	2.33 (1.90)	1.33 (1.20)	2.67 (1.84)
McAuley score	3.25 (0.22)	3.40 (0.31)	3.21 (0.22)	2.90 (0.29)

7. Secondary Outcome

Title	Augmentation Index
Description	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).
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR	4 weeks of placebo Placebo	4 weeks of placebo
Measure Participants	40	40	40	40
Least Squares Mean (Standard Error) [Percentage of pressure wave]	10.42 (1.71)	-2.0 (1.8)	12.52 (1.72)	-2.5 (1.8)

8. Secondary Outcome

Title	Heart Rate Variability (Adults)
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bromocriptine QR (Adults)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of placebo Placebo
Measure Participants	40	40
Least Squares Mean (Standard Error) [ratio]	1.09 (0.05)	1.14 (0.05)

9. Secondary Outcome

Title	Heart Rate Variability (Adolescents)
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bromocriptine QR (Adolescents)	Placebo (Adolescents)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of placebo Placebo
Measure Participants	40	40
Least Squares Mean (Standard Error) [milliseconds]	73 (5)	76.4 (4.9)

10. Secondary Outcome

Title	Sleep Duration
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of placebo Placebo	4 weeks of placebo Placebo
Measure Participants	42	42	42	42
weekdays	433 (69)	394 (59)	414 (47)	402 (62)
weekends	486 (81)	458 (95)	464 (85)	453 (98)

11. Secondary Outcome

Title	Sleep Quality
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of placebo Placebo	4 weeks of placebo Placebo
Measure Participants	42	42	42	42
efficiency during the week	87.9 (5.3)	90.4 (4.2)	89.0 (4.1)	90.4 (4.4)
efficiency weekends	88.3 (4.8)	89.7 (5.0)	89.0 (5.4)	90.9 (3.6)

12. Secondary Outcome

Title	Metabolic Markers-glucose and Triglycerides
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

glucose and triglyceride total AUC least square means +/- SD

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR	4 weeks of placebo Placebo	4 weeks of placebo
Measure Participants	42	42	42	42
Glucose	11735 (7180)	9228 (5530)	11356 (5990)	12357 (6962)
Triglycerides	3452 (2878)	3445 (4582)	3066 (2040)	3460 (4634)

13. Secondary Outcome

Title	Metabolic Markers-fatty Acids
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Non-esterified fatty acids total AUC least square means +/- SD

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR	4 weeks of placebo Placebo	4 weeks of placebo
Measure Participants	42	42	42	42
Least Squares Mean (Standard Deviation) [microEq*hr/L]	123334 (115005)	75561 (52616)	93661 (58385)	67497 (46017)

14. Secondary Outcome

Title	Metabolic Markers-glucagon
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

glucagon total AUC least square means +/- SE

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR	4 weeks of placebo Placebo	4 weeks of placebo
Measure Participants	42	42	42	42
Least Squares Mean (Standard Deviation) [pg*hr/mL]	2398 (1959)	2160 (1361)	2011 (1252)	2350 (1491)

15. Secondary Outcome

Title	Metabolic Markers - GLP1
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

GLP-1 total AUC least square means +/- SD

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR	4 weeks of placebo Placebo	4 weeks of placebo
Measure Participants	42	42	42	42
Least Squares Mean (Standard Deviation) [pmol*hr/L]	661 (435)	872 (563)	766 (392)	1196 (728)

16. Secondary Outcome

Title	Metabolic Markers - Insulin
Description	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.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

insulin total AUC least square means +/- SD

Arm/Group Title	Bromocriptine QR (Adolescents)	Bromocriptine QR (Adults)	Placebo (Adolescents)	Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine	4 weeks of investigational drug Bromocriptine QR	4 weeks of placebo Placebo	4 weeks of placebo
Measure Participants	42	42	42	42
Least Squares Mean (Standard Deviation) [microIU*hr/mL]	4162 (2496)	2386 (1087)	4001 (3209)	2379 (1160)

Adverse Events

Time Frame	6 months
Arm/Group Title	Bromocriptine QR (Adolescents)		Bromocriptine QR (Adults)		Placebo (Adolescents)		Placebo (Adults)
Arm/Group Description	4 weeks of investigational drug Bromocriptine QR Bromocriptine		4 weeks of investigational drug Bromocriptine QR Bromocriptine		4 weeks of placebo Placebo		4 weeks of placebo Placebo
All Cause Mortality
	Bromocriptine QR (Adolescents)		Bromocriptine QR (Adults)		Placebo (Adolescents)		Placebo (Adults)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/42 (2.4%)		1/42 (2.4%)		0/42 (0%)		0/42 (0%)
Serious Adverse Events
	Bromocriptine QR (Adolescents)		Bromocriptine QR (Adults)		Placebo (Adolescents)		Placebo (Adults)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/42 (2.4%)		1/42 (2.4%)		0/42 (0%)		0/42 (0%)
Endocrine disorders
severe hypoglycemia	1/42 (2.4%)	1	0/42 (0%)	0	0/42 (0%)	0	0/42 (0%)	0
Musculoskeletal and connective tissue disorders
diagnosed with RA	0/42 (0%)	0	1/42 (2.4%)	1	0/42 (0%)	0	0/42 (0%)	0
Other (Not Including Serious) Adverse Events
	Bromocriptine QR (Adolescents)		Bromocriptine QR (Adults)		Placebo (Adolescents)		Placebo (Adults)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/42 (31%)		17/42 (40.5%)		1/42 (2.4%)		3/42 (7.1%)
Gastrointestinal disorders
nausea	13/42 (31%)		17/42 (40.5%)		1/42 (2.4%)		3/42 (7.1%)
General disorders
fatigue	1/42 (2.4%)		5/42 (11.9%)		0/42 (0%)		3/42 (7.1%)
headache	2/42 (4.8%)		2/42 (4.8%)		1/42 (2.4%)		1/42 (2.4%)
Vascular disorders
orthostasis	4/42 (9.5%)		6/42 (14.3%)		0/42 (0%)		2/42 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.