Trial Outcomes & Findings for Effectiveness of Sitagliptin for HIV Insulin Resistance and Inflammation (NCT NCT01552694)
NCT ID: NCT01552694
Last Updated: 2018-05-08
Results Overview
Fasting serum and plasma samples obtained at baseline and week 8 are batched for ELISA analysis (end of sudy) of hsCRP, IL-6 and D-dimer concentrations.
COMPLETED
PHASE3
38 participants
2 months
2018-05-08
Participant Flow
38 participants were initially enrolled. 1 was lost to follow-up; 1 started a personal exercise training program while enrolled in the study. Any data collected on these 2 participants were excluded from the analysis. Both were initially enrolled in the placebo group.
36 participants completed the trial with complete data.
Participant milestones
| Measure |
Sitagliptin
100 mg sitagliptin/day for 2 months
Sitagliptin: Oral, 100 mg/day for 2 months
|
Placebo
Matching placebo daily for 2 months
Placebo: oral, matching placebo daily for 2 months
|
|---|---|---|
|
Overall Study
STARTED
|
18
|
20
|
|
Overall Study
COMPLETED
|
18
|
18
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Sitagliptin
100 mg sitagliptin/day for 2 months
Sitagliptin: Oral, 100 mg/day for 2 months
|
Placebo
Matching placebo daily for 2 months
Placebo: oral, matching placebo daily for 2 months
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
Effectiveness of Sitagliptin for HIV Insulin Resistance and Inflammation
Baseline characteristics by cohort
| Measure |
Sitagliptin
n=18 Participants
100 mg sitagliptin/day for 2 months
Sitagliptin: Oral, 100 mg/day for 2 months
|
Placebo
n=18 Participants
Matching placebo daily for 2 months
Placebo: oral, matching placebo daily for 2 months
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
49 years
STANDARD_DEVIATION 9 • n=5 Participants
|
52 years
STANDARD_DEVIATION 6 • n=7 Participants
|
51 years
STANDARD_DEVIATION 7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
2 participants
n=5 Participants
|
11 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
16 participants
n=5 Participants
|
7 participants
n=7 Participants
|
23 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
18 participants
n=7 Participants
|
36 participants
n=5 Participants
|
|
Weight
|
97 kg
STANDARD_DEVIATION 21 • n=5 Participants
|
102 kg
STANDARD_DEVIATION 29 • n=7 Participants
|
100 kg
STANDARD_DEVIATION 25 • n=5 Participants
|
|
Body mass index
|
32.7 kg/m^2
STANDARD_DEVIATION 8.2 • n=5 Participants
|
33.1 kg/m^2
STANDARD_DEVIATION 8.2 • n=7 Participants
|
32.9 kg/m^2
STANDARD_DEVIATION 8.2 • n=5 Participants
|
|
Waist circumference
|
106 cm
STANDARD_DEVIATION 19 • n=5 Participants
|
112 cm
STANDARD_DEVIATION 23 • n=7 Participants
|
109 cm
STANDARD_DEVIATION 22 • n=5 Participants
|
|
Systolic blood pressure
|
124 mmHg
STANDARD_DEVIATION 15 • n=5 Participants
|
127 mmHg
STANDARD_DEVIATION 14 • n=7 Participants
|
125 mmHg
STANDARD_DEVIATION 14 • n=5 Participants
|
|
Diastolic blood pressure
|
74 mmHg
STANDARD_DEVIATION 9 • n=5 Participants
|
78 mmHg
STANDARD_DEVIATION 10 • n=7 Participants
|
76 mmHg
STANDARD_DEVIATION 10 • n=5 Participants
|
|
HIV duration
|
14.9 years
STANDARD_DEVIATION 5.8 • n=5 Participants
|
14.2 years
STANDARD_DEVIATION 7.5 • n=7 Participants
|
14.6 years
STANDARD_DEVIATION 6.2 • n=5 Participants
|
|
CD4+ T-cell count
|
731 cells/µL
STANDARD_DEVIATION 220 • n=5 Participants
|
606 cells/µL
STANDARD_DEVIATION 218 • n=7 Participants
|
668 cells/µL
STANDARD_DEVIATION 219 • n=5 Participants
|
|
CD8+ T-cell count
|
1017 cells/µL
STANDARD_DEVIATION 542 • n=5 Participants
|
801 cells/µL
STANDARD_DEVIATION 294 • n=7 Participants
|
909 cells/µL
STANDARD_DEVIATION 418 • n=5 Participants
|
PRIMARY outcome
Timeframe: 2 monthsFasting serum and plasma samples obtained at baseline and week 8 are batched for ELISA analysis (end of sudy) of hsCRP, IL-6 and D-dimer concentrations.
Outcome measures
| Measure |
Sitagliptin
n=18 Participants
100 mg sitagliptin/day for 2 months
Sitagliptin: Oral, 100 mg/day for 2 months
|
Placebo
n=18 Participants
Matching placebo daily for 2 months
Placebo: oral, matching placebo daily for 2 months
|
|---|---|---|
|
Inflammatory Biomarker 1: Plasma hsCRP Concentration
Baseline
|
3.4 mg/L
Standard Deviation 3.2
|
5.4 mg/L
Standard Deviation 4.5
|
|
Inflammatory Biomarker 1: Plasma hsCRP Concentration
Week 8
|
2.9 mg/L
Standard Deviation 2.6
|
7.4 mg/L
Standard Deviation 5.8
|
PRIMARY outcome
Timeframe: 2 monthsThere are 3 levels of the primary outcome measure; hsCRP, IL-6, and D-dimer concentrations measured at baseline and week 8
Outcome measures
| Measure |
Sitagliptin
n=18 Participants
100 mg sitagliptin/day for 2 months
Sitagliptin: Oral, 100 mg/day for 2 months
|
Placebo
n=18 Participants
Matching placebo daily for 2 months
Placebo: oral, matching placebo daily for 2 months
|
|---|---|---|
|
Inflammatory Biomarker 2: Plasma IL-6 Concentration
Baseline
|
1.36 pg/mL
Standard Deviation 0.74
|
2.61 pg/mL
Standard Deviation 1.91
|
|
Inflammatory Biomarker 2: Plasma IL-6 Concentration
Week 8
|
1.30 pg/mL
Standard Deviation 0.55
|
2.65 pg/mL
Standard Deviation 1.83
|
PRIMARY outcome
Timeframe: 2 monthsThere are 3 levels of the primary outcome measure, hsCRP, IL-6, and D-dimer
Outcome measures
| Measure |
Sitagliptin
n=18 Participants
100 mg sitagliptin/day for 2 months
Sitagliptin: Oral, 100 mg/day for 2 months
|
Placebo
n=18 Participants
Matching placebo daily for 2 months
Placebo: oral, matching placebo daily for 2 months
|
|---|---|---|
|
Inflammatory Biomarker 3: Serum D-dimer Concentration
Baseline
|
0.32 µg FEU/mL
Standard Deviation 0.20
|
0.28 µg FEU/mL
Standard Deviation 0.15
|
|
Inflammatory Biomarker 3: Serum D-dimer Concentration
Week 8
|
0.33 µg FEU/mL
Standard Deviation 0.24
|
0.31 µg FEU/mL
Standard Deviation 0.20
|
SECONDARY outcome
Timeframe: Baseline to 2 monthsPopulation: Adipose tissue samples were not available from all participants. This secondary outcome includes fewer participants analyzed than the primary outcome.
Adipose tissue from obese, insulin resistant subjects is characterized by increased macrophage infiltration and overexpression of inflammatory cytokines/chemokines. In adipose samples, mRNA expression for the macrophage inflammation marker CCL2 (MCP-1) was quantified. Fold change between population averages from baseline to 2 months for adipose macrophage CCL2 (MCP-1) mRNA expression is the outcome measure.
Outcome measures
| Measure |
Sitagliptin
n=11 Participants
100 mg sitagliptin/day for 2 months
Sitagliptin: Oral, 100 mg/day for 2 months
|
Placebo
n=7 Participants
Matching placebo daily for 2 months
Placebo: oral, matching placebo daily for 2 months
|
|---|---|---|
|
Fold Change in Adipose Inflammation Marker CCL2 (MCP-1) mRNA Expression
|
-2.5 fold change
|
-0.4 fold change
|
SECONDARY outcome
Timeframe: Baseline to 2 monthsPopulation: CD34+/VEGFR2+/KDR+ monocytes (EPC) are a very rare cell type (\<1% of PBMC). Not all blood samples contain EPC cells, or there are too few to count reliably. This measure was obtained in a subset of the total participants.
Monocytes (PBMC) are isolated from 20 mL blood. CD34+/VEGFR2+/KDR+ monocytes represent cell markers for endothelial progenitor cells (EPC). CD34+/VEGFR2+/KDR+ monocytes are counted (flow cytometry) and expressed as a percentage of PBMC number. Percent change between population averages from baseline to 2 months for the EPC/PBMC ratio is calculated and reported as the outcome measure.
Outcome measures
| Measure |
Sitagliptin
n=12 Participants
100 mg sitagliptin/day for 2 months
Sitagliptin: Oral, 100 mg/day for 2 months
|
Placebo
n=11 Participants
Matching placebo daily for 2 months
Placebo: oral, matching placebo daily for 2 months
|
|---|---|---|
|
Percent Change in Blood Endothelial Progenitor Cells
|
0.3 Percent change
|
-0.2 Percent change
|
Adverse Events
Sitagliptin
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sitagliptin
n=18 participants at risk
100 mg sitagliptin/day for 2 months
Sitagliptin: Oral, 100 mg/day for 2 months
|
Placebo
n=20 participants at risk
Matching placebo daily for 2 months
Placebo: oral, matching placebo daily for 2 months
|
|---|---|---|
|
General disorders
Fatique, Fever, Chills, Loss of appetite, Weight Loss
|
44.4%
8/18 • Number of events 9
|
35.0%
7/20 • Number of events 7
|
|
Infections and infestations
Sinus, respiratoy urinary tract infections
|
11.1%
2/18 • Number of events 2
|
15.0%
3/20 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Rash, pruritus, easy bruising
|
16.7%
3/18 • Number of events 3
|
15.0%
3/20 • Number of events 3
|
|
Cardiac disorders
Chest pain, shortness of breath, wheezing, cough
|
16.7%
3/18 • Number of events 3
|
20.0%
4/20 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal pain, nausea, vomiting, constipation, diarrhea, hypoglycemia
|
16.7%
3/18 • Number of events 3
|
30.0%
6/20 • Number of events 6
|
|
Renal and urinary disorders
Chnages in urinary frequency, painful urination, blood in urine
|
11.1%
2/18 • Number of events 2
|
15.0%
3/20 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
muscle ache, arthritis, swelling, weakness
|
22.2%
4/18 • Number of events 4
|
25.0%
5/20 • Number of events 5
|
|
Nervous system disorders
headaches, dizziness ,numbness, depression, anxiety, confusion
|
22.2%
4/18 • Number of events 8
|
25.0%
5/20 • Number of events 10
|
Additional Information
Kevin Yarasheski, PhD
Washington University School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place