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| ID | Type | Description | Link |
|---|---|---|---|
| UL1TR001082 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Juvenile Diabetes Research Foundation | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bromocriptine QR | Active Comparator | 4 weeks of investigational drug Bromocriptine QR |
|
| Placebo | Placebo Comparator | 4 weeks of placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bromocriptine | Drug |
|
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Irene Schauer, MD, PhD | University of Colorado, Denver | Principal Investigator |
| Kristen Nadeau, MD, MS | Children's Hospital Colorado/University of Colorado | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado-Denver, Anshutz Medical Campus | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35712800 | Derived | 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. |
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Some participants screen failed or withdrew from the study after enrollment, but prior to starting the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Bromocriptine QR, Then Placebo | 4 weeks of investigational drug Bromocriptine QR, then 4 weeks of placebo. |
| FG001 | Placebo, Then Bromocriptine QR | 4 weeks of placebo, then 4 weeks of investigational drug Bromocriptine QR |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Includes all subjects who completed at least one phase of the study
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| ID | Title | Description |
|---|---|---|
| BG000 | Bromocriptine QR, Then Placebo | 4 weeks of investigational drug Bromocriptine QR, then 4 weeks of placebo. |
| BG001 | Placebo, Then Bromocriptine QR | 4 weeks of placebo, then 4 weeks of investigational drug Bromocriptine QR |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Adults and adolescents are divided by rows |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Data reflects average glucose levels. | Posted | Least Squares Mean | Standard Error | mg/dl | 4 weeks |
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bromocriptine QR (Adolescents) | 4 weeks of investigational drug Bromocriptine QR Bromocriptine |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| severe hypoglycemia | Endocrine disorders | Non-systematic Assessment | participant had episode of severe hypoglycemia working at high altitude as a diabetes camp counselor without adjusting insulin dosing as instructed for the change in altitude/activity Event resolved without sequelae. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea | Gastrointestinal disorders | Non-systematic Assessment | shortly after dose. only caused one w/d. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Irene Schauer, MD | University of Colorado Denver | 3037241111 | clinicalresearchsupportcenter@ucdenver.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 29, 2018 | May 27, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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Not provided
| ID | Term |
|---|---|
| D001971 | Bromocriptine |
| ID | Term |
|---|---|
| D004879 | Ergotamines |
| D004876 | Ergot Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Other |
|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Protocol Violation |
|
| BG002 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Adults and adolescents are divided by rows | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Adults and adolescents are divided by rows | Count of Participants | Participants |
|
| Race (NIH/OMB) | Adults and adolescents are divided by rows | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Placebo (Adolescents) |
4 weeks of placebo Placebo |
| OG003 | Placebo (Adults) | 4 weeks of placebo Placebo |
|
|
| 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) | Posted | Least Squares Mean | Standard Error | 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). | Compared for placebo versus BCQR after 4 weeks of treatment. | Posted | Least Squares Mean | Standard Error | %/mmHg | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | 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. | Posted | Least Squares Mean | Standard Error | mg/dl | 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. | Unadjusted least square means by mixed procedure. | Posted | Least Squares Mean | Standard Error | score on a scale | 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). | Posted | Least Squares Mean | Standard Error | Percentage of pressure wave | 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. | Posted | Least Squares Mean | Standard Error | ratio | 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. | Posted | Least Squares Mean | Standard Error | milliseconds | 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. | Posted | Mean | Standard Deviation | minutes | 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. | Posted | Mean | Standard Deviation | percent | 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. | glucose and triglyceride total AUC least square means +/- SD | Posted | Least Squares Mean | Standard Deviation | mg*hr/dL | 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. | Non-esterified fatty acids total AUC least square means +/- SD | Posted | Least Squares Mean | Standard Deviation | microEq*hr/L | 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. | glucagon total AUC least square means +/- SE | Posted | Least Squares Mean | Standard Deviation | pg*hr/mL | 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. | GLP-1 total AUC least square means +/- SD | Posted | Least Squares Mean | Standard Deviation | pmol*hr/L | 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. | insulin total AUC least square means +/- SD | Posted | Least Squares Mean | Standard Deviation | microIU*hr/mL | 4 weeks |
|
|
|
| 1 |
| 42 |
| 1 |
| 42 |
| 13 |
| 42 |
| EG001 | Bromocriptine QR (Adults) | 4 weeks of investigational drug Bromocriptine QR Bromocriptine | 1 | 42 | 1 | 42 | 17 | 42 |
| EG002 | Placebo (Adolescents) | 4 weeks of placebo Placebo | 0 | 42 | 0 | 42 | 1 | 42 |
| EG003 | Placebo (Adults) | 4 weeks of placebo Placebo | 0 | 42 | 0 | 42 | 3 | 42 |
|
| diagnosed with RA | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
|
| orthostasis | Vascular disorders | Non-systematic Assessment | occurred shortly after dosing. not sever enough to cause d/c. |
|
| fatigue | General disorders | Non-systematic Assessment |
|
| headache | General disorders | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D004873 |
| Ergolines |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Male |
|
| Unknown or Not Reported |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Clarke method scores |
|
| McAuley score |
|
| weekends |
|
| efficiency weekends |
|
| Triglycerides |
|