Diabetes Mellitus, Human Immunodeficiency Virus Infection
Conditions
Keywords
HIV, Diabetes
Brief summary
This pilot study will evaluate the effects of the anti-diabetic drug Bydureon (exenatide extended-release formulation) on blood sugar levels and serum markers of inflammation in a cohort of 12 HIV-infected adults on combination antiretroviral therapy (cART) with untreated diabetes mellitus. Previous studies have shown that high levels of persistent systemic inflammation predict the development of cardiovascular and metabolic diseases in HIV-infected persons on cART (a group at very high risk of atherosclerosis and myocardial infarction). Bydureon has demonstrated potent anti-inflammatory effects in prior studies of non-HIV infected persons, which suggests that this agent may represent a unique and preferred medication for the treatment of insulin resistance in HIV-infected adults. The Investigators hypothesize that short-term (16 weeks) therapy with Bydureon will improve glucose tolerance and significantly reduce circulating plasma levels of interleukin-6 (IL-6) and highly-sensitive C-reactive protein (hsCRP), two biomarkers strongly implicated in the development of cardiovascular and metabolic diseases in diabetic, HIV-infected, cART-treated adults.
Detailed description
No further information. This was a single-arm trial to add an additional anti-diabetic medication to patients already known to be diabetic. The primary endpoint assessed whether the intervention reduced inflammation. There was no control arm.
Interventions
DRUGextended-release exenatide
Single arm study - 2mg Bydureon every 7 days x 16 weeks
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Vanderbilt University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Body mass index ≥ 25 kg/m2 * Glycosylated hemoglobin (A1C) value ≥ 6.5% OR having a fasting blood glucose ≥ 126 mg/dL * On stable antiretroviral therapy for ≥ 12 months (with a fully suppressed plasma HIV-1 RNA level) * Negative serum pregnancy test (females only)
Exclusion criteria
* History of pancreatitis * Screening serum lipase value greater than or equal to 2 times the upper limit of normal (≥ 420 U/L) * History of pancreatic cancer or thyroid cancer in patient, a first-degree relative, or a grandparent * History of Multiple Endocrine Neoplasia (MEN) 2 syndrome * History of gastroparesis, inflammatory bowel disease, and/or other severe gastrointestinal disease * Estimated glomerular filtration rate (eGFR) ≤ 50 mls/minute * Documented history of hypoglycemia (blood glucose \<40 mg/dl) * Active moderate-heavy alcohol use (more than 2 drinks/day) or \>4 drinks in a single 24 hour period * On an anti-diabetic medication within 3 months of enrollment * On an HMG-CoA reductase inhibitor (statin) within 3 months of enrollment * Persons on a didanosine (ddI) and/or stavudine (d4T)-containing cART (due to the heightened risk of pancreatitis)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Interleukin 6 (IL-6) at Levels at Baseline and 16 Weeks | baseline and 16 weeks | The primary outcome will be the change in serum IL-6 levels from baseline (pre-treatment) to 16 weeks of Bydureon treatment. |
| Serum Highly-sensitive C-reactive Protein (hsCRP) Levels at Baseline and 16 Weeks | baseline and 16 weeks | The primary outcome will be the change in hsCRP levels from baseline (pre-treatment) to 16 weeks of Bydureon treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Macrophage Chemotactic Protein-1 (MCP-1) Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Serum Macrophage Inflammatory Protein 1 Alpha (MIP-1 Alpha) Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Oral Glucose Insulin Sensitivity (OGIS) at Baseline and 16 Weeks | baseline and 16 weeks | The Oral Glucose Insulin Sensitivity (OGIS) is a method for the assessment of insulin sensitivity from the oral glucose tolerance test. OGIS provides an index which is analogous to the index of insulin sensitivity obtained from the glucose clamp. OGIS values for glucose clearance are reported in units of ml/min per square meter of body surface area. Lower values indicate slower glucose clearance and higher insulin resistance. |
| Serum Adipokine Leptin Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Body Mass Index at Baseline and 16 Weeks | 16 weeks | — |
| Serum TNF-a Receptor 1 Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Serum Soluble CD14 Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Serum TNF-a Receptor 2 Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Serum Triglycerides Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Serum Total Cholesterol Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Serum HDL Cholesterol Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Serum LDL Cholesterol Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Body Weight at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Waist Circumference at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Hip Circumference at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Waist to Hip Ratio at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Serum Hemoglobin A1c (HbA1c) Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
| Serum Soluble Tumor Necrosis Factor Alpha (TNF-α) Levels at Baseline and 16 Weeks | baseline and 16 weeks | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Peripheral Endothelial Tonography, as Measured by the Non-invasive EndoPAT System Using the LnRHI (Natural Log of Reactive Hyperemia Index), at Baseline and 16 Weeks | baseline and 16 weeks | Normal: LnRHI \> 0.51 Abnormal: LnRHI ≤ 0.51 |
Countries
United States
Participant flow
Recruitment details
Six HIV-infected participants recruited from the Vanderbilt Comprehensive Care Clinic between April 17, 2013 and May 6, 2016.
Pre-assignment details
No consented participants were excluded prior to group assignment
Participants by arm
| Arm | Count |
|---|---|
| Bydureon Treatment Treatment for 16 weeks with extended-release Exenatide (Bydureon) extended-release exenatide | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Bydureon Treatment |
|---|---|
| Age, Continuous | 51 years |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Serum Highly-sensitive C-reactive Protein (hsCRP) Levels at Baseline and 16 Weeks
The primary outcome will be the change in hsCRP levels from baseline (pre-treatment) to 16 weeks of Bydureon treatment.
Time frame: baseline and 16 weeks
Population: Change in hsCRP over 16 weeks of treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Bydureon Treatment | Serum Highly-sensitive C-reactive Protein (hsCRP) Levels at Baseline and 16 Weeks | baseline | 4.0 mg/dl |
| Bydureon Treatment | Serum Highly-sensitive C-reactive Protein (hsCRP) Levels at Baseline and 16 Weeks | 16 weeks | 5.6 mg/dl |
p-value: 0.08Wilcoxon (Mann-Whitney)
Primary
Serum Interleukin 6 (IL-6) at Levels at Baseline and 16 Weeks
The primary outcome will be the change in serum IL-6 levels from baseline (pre-treatment) to 16 weeks of Bydureon treatment.
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Bydureon Treatment | Serum Interleukin 6 (IL-6) at Levels at Baseline and 16 Weeks | baseline | 1.07 mg/dl |
| Bydureon Treatment | Serum Interleukin 6 (IL-6) at Levels at Baseline and 16 Weeks | week 16 | 1.27 mg/dl |
Comparison: The null hypothesis was that there would be no difference between baseline and 16 week IL-6p-value: 0.34Wilcoxon (Mann-Whitney)
Secondary
Body Mass Index at Baseline and 16 Weeks
Time frame: 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Body Mass Index at Baseline and 16 Weeks | baseline | 32.6 kg/m2 |
| Bydureon Treatment | Body Mass Index at Baseline and 16 Weeks | 16 weeks | 31.3 kg/m2 |
p-value: 0.03Wilcoxon (Mann-Whitney)
Secondary
Body Weight at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Body Weight at Baseline and 16 Weeks | baseline | 100 kilograms |
| Bydureon Treatment | Body Weight at Baseline and 16 Weeks | 16 weeks | 96 kilograms |
p-value: 0.046Wilcoxon (Mann-Whitney)
Secondary
Hip Circumference at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Hip Circumference at Baseline and 16 Weeks | baseline | 107 centimeters |
| Bydureon Treatment | Hip Circumference at Baseline and 16 Weeks | 16 weeks | 103 centimeters |
p-value: 0.12Wilcoxon (Mann-Whitney)
Secondary
Oral Glucose Insulin Sensitivity (OGIS) at Baseline and 16 Weeks
The Oral Glucose Insulin Sensitivity (OGIS) is a method for the assessment of insulin sensitivity from the oral glucose tolerance test. OGIS provides an index which is analogous to the index of insulin sensitivity obtained from the glucose clamp. OGIS values for glucose clearance are reported in units of ml/min per square meter of body surface area. Lower values indicate slower glucose clearance and higher insulin resistance.
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Oral Glucose Insulin Sensitivity (OGIS) at Baseline and 16 Weeks | baseline | 310 ml/min/m^2 BSA |
| Bydureon Treatment | Oral Glucose Insulin Sensitivity (OGIS) at Baseline and 16 Weeks | 16 weeks | 399 ml/min/m^2 BSA |
p-value: 0.47Wilcoxon (Mann-Whitney)
Secondary
Serum Adipokine Leptin Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum Adipokine Leptin Levels at Baseline and 16 Weeks | baseline | 17.4 ng/ml |
| Bydureon Treatment | Serum Adipokine Leptin Levels at Baseline and 16 Weeks | 16 weeks | 14.3 ng/ml |
p-value: 0.92Wilcoxon (Mann-Whitney)
Secondary
Serum HDL Cholesterol Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum HDL Cholesterol Levels at Baseline and 16 Weeks | baseline | 39 mg/dL |
| Bydureon Treatment | Serum HDL Cholesterol Levels at Baseline and 16 Weeks | 16 weeks | 34 mg/dL |
p-value: 0.42Wilcoxon (Mann-Whitney)
Secondary
Serum Hemoglobin A1c (HbA1c) Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum Hemoglobin A1c (HbA1c) Levels at Baseline and 16 Weeks | baseline | 7.6 percentage of glycated haemoglobin |
| Bydureon Treatment | Serum Hemoglobin A1c (HbA1c) Levels at Baseline and 16 Weeks | 16 weeks | 6.3 percentage of glycated haemoglobin |
p-value: 0.07Wilcoxon (Mann-Whitney)
Secondary
Serum LDL Cholesterol Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum LDL Cholesterol Levels at Baseline and 16 Weeks | baseline | 127 mg/dL |
| Bydureon Treatment | Serum LDL Cholesterol Levels at Baseline and 16 Weeks | 16 weeks | 109 mg/dL |
p-value: 0.89Wilcoxon (Mann-Whitney)
Secondary
Serum Macrophage Chemotactic Protein-1 (MCP-1) Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum Macrophage Chemotactic Protein-1 (MCP-1) Levels at Baseline and 16 Weeks | baseline | 5.73 pg/ml |
| Bydureon Treatment | Serum Macrophage Chemotactic Protein-1 (MCP-1) Levels at Baseline and 16 Weeks | 16 weeks | 4.78 pg/ml |
p-value: 0.92Wilcoxon (Mann-Whitney)
Secondary
Serum Macrophage Inflammatory Protein 1 Alpha (MIP-1 Alpha) Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum Macrophage Inflammatory Protein 1 Alpha (MIP-1 Alpha) Levels at Baseline and 16 Weeks | baseline | 0.088 pg/ml |
| Bydureon Treatment | Serum Macrophage Inflammatory Protein 1 Alpha (MIP-1 Alpha) Levels at Baseline and 16 Weeks | 16 weeks | 0.081 pg/ml |
p-value: 0.69Wilcoxon (Mann-Whitney)
Secondary
Serum Soluble CD14 Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum Soluble CD14 Levels at Baseline and 16 Weeks | baseline | 598 pg/ml |
| Bydureon Treatment | Serum Soluble CD14 Levels at Baseline and 16 Weeks | 16 weeks | 671 pg/ml |
p-value: 0.08Wilcoxon (Mann-Whitney)
Secondary
Serum Soluble Tumor Necrosis Factor Alpha (TNF-α) Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum Soluble Tumor Necrosis Factor Alpha (TNF-α) Levels at Baseline and 16 Weeks | baseline | 2.44 pg/ml |
| Bydureon Treatment | Serum Soluble Tumor Necrosis Factor Alpha (TNF-α) Levels at Baseline and 16 Weeks | 16 weeks | 2.82 pg/ml |
p-value: 0.046Wilcoxon (Mann-Whitney)
Secondary
Serum TNF-a Receptor 1 Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum TNF-a Receptor 1 Levels at Baseline and 16 Weeks | baseline | 392 pg/ml |
| Bydureon Treatment | Serum TNF-a Receptor 1 Levels at Baseline and 16 Weeks | 16 weeks | 399 pg/ml |
p-value: 0.6Wilcoxon (Mann-Whitney)
Secondary
Serum TNF-a Receptor 2 Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum TNF-a Receptor 2 Levels at Baseline and 16 Weeks | baseline | 598 pg/ml |
| Bydureon Treatment | Serum TNF-a Receptor 2 Levels at Baseline and 16 Weeks | 16 weeks | 671 pg/ml |
p-value: 0.08Wilcoxon (Mann-Whitney)
Secondary
Serum Total Cholesterol Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum Total Cholesterol Levels at Baseline and 16 Weeks | baseline | 192 mg/dL |
| Bydureon Treatment | Serum Total Cholesterol Levels at Baseline and 16 Weeks | 16 weeks | 176 mg/dL |
p-value: 0.5Wilcoxon (Mann-Whitney)
Secondary
Serum Triglycerides Levels at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Serum Triglycerides Levels at Baseline and 16 Weeks | baseline | 172 mg/dL |
| Bydureon Treatment | Serum Triglycerides Levels at Baseline and 16 Weeks | 16 weeks | 118 mg/dL |
p-value: 0.69Wilcoxon (Mann-Whitney)
Secondary
Waist Circumference at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Waist Circumference at Baseline and 16 Weeks | baseline | 113 centimeters |
| Bydureon Treatment | Waist Circumference at Baseline and 16 Weeks | 16 weeks | 113 centimeters |
p-value: 0.25Wilcoxon (Mann-Whitney)
Secondary
Waist to Hip Ratio at Baseline and 16 Weeks
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Waist to Hip Ratio at Baseline and 16 Weeks | baseline | 1.06 ratio |
| Bydureon Treatment | Waist to Hip Ratio at Baseline and 16 Weeks | 16 weeks | 1.06 ratio |
p-value: 0.046Wilcoxon (Mann-Whitney)
Other Pre-specified
Peripheral Endothelial Tonography, as Measured by the Non-invasive EndoPAT System Using the LnRHI (Natural Log of Reactive Hyperemia Index), at Baseline and 16 Weeks
Normal: LnRHI \> 0.51 Abnormal: LnRHI ≤ 0.51
Time frame: baseline and 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bydureon Treatment | Peripheral Endothelial Tonography, as Measured by the Non-invasive EndoPAT System Using the LnRHI (Natural Log of Reactive Hyperemia Index), at Baseline and 16 Weeks | baseline | 0.71 units on a scale |
| Bydureon Treatment | Peripheral Endothelial Tonography, as Measured by the Non-invasive EndoPAT System Using the LnRHI (Natural Log of Reactive Hyperemia Index), at Baseline and 16 Weeks | 16 weeks | 0.62 units on a scale |
p-value: 0.75Wilcoxon (Mann-Whitney)