Diabetes Mellitus, Type 2
Conditions
Brief summary
QR-Bromocriptine as an add-on treatment to insulin and metformin in the management of type 2 diabetes will result in improved glycemic control, reduced exogenous insulin requirement, increased lean fat mass and improved pancreatic beta-cell function.
Detailed description
To assess improvement in glycemic control, reliance on exogenous insulin, improvements in lean body mass composition, and improvements in pancreatic beta-cell function.
Interventions
DRUGQR-bromocriptine
The study drug is added-on to patients on existing type 2 diabetes treatment with insulin +metformin+exercise/nutritional counseling. The study drug is titrated up starting at one 0.8mg tab daily for 1 week, then 2 (0.8mg) tablets for week 2, then 3 tablets for week 3, then 4 tablets for week 4, then 5 tablets for week 5, then six tablets for week 6 (total 4.8). The limiting factor is nausea at which point the patients will back down the highest tolerated dose and continue on that dose for the remainder of the 6 months of the study.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male and female patients, age 30 to 65 years of age, 2. Clinical diagnosis of type 2 diabetes at least 6 months prior to enrollment, 3. Stable on current treatment consisting of either human or recombinant multi-dose insulin therapy (MDI) with metformin, 4. HbA1c of 7.5-12%, inclusive, 5. Demonstrated willingness to check and record blood glucose readings at seven time points as instructed in the study protocol. 6. Medically controlled hypertension, at least on one anti-hypertensive 7. Medically controlled hyperlipidemia, on or off cholesterol-lowering therapy 8. BMI \>30
Exclusion criteria
1. Pregnancy or Lactating, 2. Type 1 Diabetes, 3. Concomitant use of forbidden medications: prescription sympathomimetics (within seven days of screening), ergot alkaloid derivatives, and anti-migraine medications, 4. Patients with history of drug or alcohol abuse within 3 years of enrollment, 5. Patients at risk for hypotension, including those who have: * Recent blood donation within 30 days of enrollment, * A history of syncopal migraines, or * Significant gastroparesis or orthostatic hypotension which could signify advanced autonomic neuropathy. 6. Uncontrolled mental illness especially with history of psychosis, 7. Any severe, uncontrolled or terminal medical condition which the investigator feels would interfere with the patient's ability to participate and comply with the study protocol, 8. Serum creatinine \>1.4mg/dL in females or \>1.5mg/dL in males that would preclude the patient from taking metformin, 9. LFTs elevated \>3x upper limit of normal, 10. Patients working rotating, varying or night shifts, or 11. Patient with circumstances or abnormalities (e.g. blindness or history of non-compliance) that would interfere with the interpretation of safety or efficacy data or completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in A1c | Baseline - 24 weeks | Change from baseline HbA1c between subjects receiving QR-Bromocriptine + metformin + insulin compared to those subjects receiving metformin + insulin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Daily Insulin Dose | Baseline - 24 weeks | Change in total daily insulin dose in patients treated with QR-Bromocriptine +metformin +insulin compared to metformin + insulin alone |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metformin + Insulin 5 patients to continue on usual type 2 diabetic treatment consisting of 70/30 insulin, metformin and exercise and nutrition counseling.
No Change | 5 |
| QR-Bromocriptine +Metformin+Insulin study drug add-on the usual therapy
QR-bromocriptine: The study drug is added-on to patients on existing type 2 diabetes treatment with insulin +metformin+exercise/nutritional counseling. The study drug is titrated up starting at one 0.8mg tab daily for 1 week, then 2 (0.8mg) tablets for week 2, then 3 tablets for week 3, then 4 tablets for week 4, then 5 tablets for week 5, then six tablets for week 6 (total 4.8). The limiting factor is nausea at which point the patients will back down the highest tolerated dose and continue on that dose for the remainder of the 6 months of the study. | 10 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | QR-Bromocriptine +Metformin+Insulin | Metformin + Insulin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 5 Participants | 15 Participants |
| Age, Continuous | 54 years STANDARD_DEVIATION 3 | 46 years STANDARD_DEVIATION 3 | 50 years STANDARD_DEVIATION 2 |
| Region of Enrollment United States | 10 participants | 5 participants | 15 participants |
| Sex: Female, Male Female | 9 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 7 |
| serious Total, serious adverse events | 0 / 5 | 0 / 7 |
Outcome results
Primary
Change in A1c
Change from baseline HbA1c between subjects receiving QR-Bromocriptine + metformin + insulin compared to those subjects receiving metformin + insulin
Time frame: Baseline - 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin + Insulin | Change in A1c | 9.74 percent HbA1c | Standard Error 0.56 |
| QR-Bromocriptine + Metformin + Insulin | Change in A1c | 7.98 percent HbA1c | Standard Error 0.36 |
p-value: 0.004ANOVA
Secondary
Total Daily Insulin Dose
Change in total daily insulin dose in patients treated with QR-Bromocriptine +metformin +insulin compared to metformin + insulin alone
Time frame: Baseline - 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin + Insulin | Total Daily Insulin Dose | 199 units of insulin | Standard Error 33 |
| QR-Bromocriptine + Metformin + Insulin | Total Daily Insulin Dose | 147 units of insulin | Standard Error 31 |
p-value: 0.01ANOVA
p-value: 0.009ANOVA