InflammationPhase 3NCT01552694
Effectiveness of Sitagliptin for HIV Insulin Resistance and Inflammation
A Phase 3 study testing Sitagliptin in people with Inflammation and Macrophage Infiltration, run by Washington University School of Medicine at 1 site in United States.
Trial summary
People living with human immunodeficiency virus infection (HIV) have 2-4fold greater risk for developing diabetes and heart disease than the general population. They need safe and effective treatments that reduce the risk for developing diabetes and heart disease, and improve their quality of life. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Inflammation, Macrophage Infiltration, Cardiovascular Disease
- What is being tested?
- Sitagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Dec 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-65 yr old HIV infected men and women.
- Stable (at least the past 6 months) on combined antiretroviral therapy (cART).
- Stable immune (> 300 CD4+ T-cells/µL) and virologic (< 50 copies HIV RNA/mL) status.
- Insulin resistant/impaired glucose tolerance (fasting glucose 100-125mg/dL, or 2-hr glucose 140-200mg/dL or fasting HOMA-IR= 2.5-6.0).
- Waist circumference > 102 cm (men), > 88 cm (women).
- BMI > 20 kg/m2.
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- Fasting hypertriglyceridemia > 150 mg/dL.
- Low HDL-cholesterol (< 40 mg/dL in men or < 50 mg/dL in women).
- Platelet count > 30,000/mm3.
- Absolute neutrophil count > 750/mm3.
- Transaminases < 2.5x the upper limit of normal.
- Long-term non-progressors (not taking anti-HIV medications) are not eligible.
Who cannot join
- Diabetes (T2DM, IDDM or diabetic ketoacidosis) or taking any glucose-lowering medication (e.g., insulin, TZDs, metformin, sulfonylurea).
- Any agent that might artifactually alter glycemic control (e.g., glucocorticoids, megace, rhGH, GH-secretagogue, testosterone derivatives, creatine monohydrate, chromium picolinate, AA/protein supplements, medium- or long-chain fatty acids) during 6 months prior to or during enrollment.
- History of serious CV disease. NYHA Functional Class III or IV (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, stroke, resting hypertension > 160/95 mmHg), irregular heart rhythm, resting ST-segment depression > 1mm). Treatment with medications for CV condition (e.g., α- or ß-blockers). Some BP-lowering medications (Ca++channel blocker, diuretic, or ACE inhibitor) are permitted.
- Moderate to severe renal insufficiency. Serum creatinine > 1.7 mg/dL (men) > 1.5 mg/dL (women).
- Plan or anticipate a change in anti-HIV medications during the study.
- Lipid-lowering medications are permitted (fibrate or statin or niacin), but must be stable on that agent for at least 6 months prior to enrollment. Lipid-lowering agents cannot be started during the treatment period.
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- Chronic hepatitis B (HBV-surface antigen positive). Active hepatitis C (detectable Hep C RNA).
- Positive urine drug test for opiates, methamphetamine, heroin, cocaine. Active substance abuse that the MD-scientist believes may compromise safety, compliance, interfere with study drug or data interpretation.
- Hematocrit < 34% in men or < 25% in women with symptoms (fatigue, "tired-legs", shortness of breath). Hemoglobin < 10 gm/dL with symptoms.
- Pregnant or nursing mothers. Women must agree to use an acceptable form of birth control during the study. If using birth control pills-must be stable on this medication for at least 6 months prior to enrollment.
- Active malignancy or treatment with chemotherapeutic agents or radiation therapy or any cytokine or anti-cytokine therapy during 6 months prior to enrollment.
- History of pancreatitis
- > 10% unintentional weight loss during the 6 months prior to enrollment.
- Reduced cognitive function/unable to provide voluntary informed consent. Prisoners are excluded.
- Blinded investigational drugs for 3 months prior to enrollment that will not be unblinded before enrollment.
- Nausea, vomiting, diarrhea (> 4 loose stools/day) that are unresponsive to treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Double Blind, Randomized, Placebo Controlled Study to Determine the Physiological Effectiveness of Januvia for Reducing Inflammation and Increasing EPC Number in HIV Infected Men and Women With Insulin Resistance and Central Adiposity.
People living with human immunodeficiency virus infection (HIV) have 2-4fold greater risk for developing diabetes and heart disease than the general population. They need safe and effective treatments that reduce the risk for developing diabetes and heart disease, and improve their quality of life. This project will explore whether a new anti-diabetes medication (Januvia) with a novel mechanism of action reduces inflammation, and improves blood vessel function in HIV infected men and women with several risk factors for developing cardiovascular disease.
Read the detailed description
People living with human immunodeficiency virus (HIV+) infection have a 2-fold greater prevalence and incidence of T2DM and cardiovascular disease (CVD) than the general population. The investigators lack safe and effective treatments for these HIV related cardiometabolic complications despite the fact that HIV infected adults represent an ideal clinical population in which to study interactions among chronic low-grade pro-inflammatory processes that are linked to the development of adipose accumulation, insulin resistance, ß-cell secretory failure, vascular endothelial dysfunction, atherosclerosis and CVD. Dipeptidyl peptidase-IV (DPP4)-inhibitors represent a new drug class that safely and effectively regulate glycemia in T2DM, but have not been adequately tested in HIV. Of note, pre-clinical studies suggest that DPP4-inhibitors have several pleiotropic actions that may specifically benefit people living with HIV infection. For example, DPP4 inhibition reduced adipose macrophage infiltration \& inflammation and increased the number of bone-derived endothelial progenitor cells in the circulation. Our preliminary findings indicate that DPP4 inhibition is virologically and immunologically safe in non-diabetic HIV+ adults taking combination antiretroviral therapy (in preparation), but the potential pleiotropic benefits have not been examined in HIV. The investigators propose a randomized, double blind, placebo controlled physiological study to test 2 potential pleiotropic benefits of DPP4 inhibition (100 mg sitagliptin/d, 8 wk): reduce circulating and adipose-specific markers of inflammation; and increase endothelial progenitor cell numbers used for vascular repair in 36 HIV+ adults with insulin resistance, central adiposity and CVD risk factors. The investigators hypothesize that sitagliptin will reduce circulating cytokine levels, reduce adipose tissue macrophage number and inflammation, and increase the number of circulating endothelial progenitor cells in HIV infected men and women. These physiological studies will advance our understanding about the efficacy of DPP4 inhibition in this high-risk group, and may help prevent the inexorable transition from insulin resistance to T2DM and CVD in HIV infected men and women.
- Being tested
- Sitagliptin, Placebo
- Keywords
- cardiometabolic complications
- Medical subject headings
- Inflammation, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitagliptinDrug
Also called Januvia
Oral, 100 mg/day for 2 months
PlaceboDrug
oral, matching placebo daily for 2 months
| Study group | Role | What they receive |
|---|---|---|
| Sitagliptin | Experimental | 100 mg sitagliptin/day for 2 months Receives: Drug: Sitagliptin |
| Placebo | Placebo comparator | Matching placebo daily for 2 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inflammatory Biomarker 1: Plasma hsCRP Concentration
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.
Measured: 2 months
Inflammatory Biomarker 2: Plasma IL-6 Concentration
There are 3 levels of the primary outcome measure; hsCRP, IL-6, and D-dimer concentrations measured at baseline and week 8
Measured: 2 months
Inflammatory Biomarker 3: Serum D-dimer Concentration
There are 3 levels of the primary outcome measure, hsCRP, IL-6, and D-dimer
Measured: 2 months
Secondary outcomes (2)
Fold Change in Adipose Inflammation Marker CCL2 (MCP-1) mRNA Expression
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.
Measured: Baseline to 2 months
Percent Change in Blood Endothelial Progenitor Cells
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.
Measured: Baseline to 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2012 (estimated)
- Study startOct 2012
- Primary completionOct 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InflammationStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kevin Yarasheski, PhD, Washington University School of Medicine
- Investigators
- Kevin E Yarasheski, PhD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01552694
- Sponsor's protocol ID
- 41052
- Other IDs
- 41052
- Status last verified
- Mar 2018
- First submitted
- 8 Mar 2012
- Last updated
- 8 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Best C, Struthers H, Laciny E, Royal M, Reeds DN, Yarasheski KE. Sitagliptin Reduces Inflammation and Chronic Immune Cell Activation in HIV+ Adults With Impaired Glucose Tolerance. J Clin Endocrinol Metab. 2015 Jul;100(7):2621-9. doi: 10.1210/jc.2015-1531. Epub 2015 May 4.
PubMed 25938633
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind, Randomized, Placebo Controlled Study to Determine the Physiological Effectiveness of Januvia for Reducing Inflammation and Increasing EPC Number in HIV Infected Men and Women With Insulin Resistance and Central Adiposity.
- ClinicalTrials.gov ID
- NCT01552694
- Acronym / sponsor ID
- 41052
- Keywords
- cardiometabolic complications
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Oct 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 13 Mar 2012 (estimated)
- Results
- Posted 5 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
People living with human immunodeficiency virus infection (HIV) have 2-4fold greater risk for developing diabetes and heart disease than the general population. They need safe and effective treatments that reduce the risk for developing diabetes and heart disease, and improve their quality of life. This project will explore whether a new anti-diabetes medication (Januvia) with a novel mechanism of action reduces inflammation, and improves blood vessel function in HIV infected men and women with several risk factors for developing cardiovascular disease.
Detailed description
People living with human immunodeficiency virus (HIV+) infection have a 2-fold greater prevalence and incidence of T2DM and cardiovascular disease (CVD) than the general population. The investigators lack safe and effective treatments for these HIV related cardiometabolic complications despite the fact that HIV infected adults represent an ideal clinical population in which to study interactions among chronic low-grade pro-inflammatory processes that are linked to the development of adipose accumulation, insulin resistance, ß-cell secretory failure, vascular endothelial dysfunction, atherosclerosis and CVD. Dipeptidyl peptidase-IV (DPP4)-inhibitors represent a new drug class that safely and effectively regulate glycemia in T2DM, but have not been adequately tested in HIV. Of note, pre-clinical studies suggest that DPP4-inhibitors have several pleiotropic actions that may specifically benefit people living with HIV infection. For example, DPP4 inhibition reduced adipose macrophage infiltration \& inflammation and increased the number of bone-derived endothelial progenitor cells in the circulation. Our preliminary findings indicate that DPP4 inhibition is virologically and immunologically safe in non-diabetic HIV+ adults taking combination antiretroviral therapy (in preparation), but the potential pleiotropic benefits have not been examined in HIV. The investigators propose a randomized, double blind, placebo controlled physiological study to test 2 potential pleiotropic benefits of DPP4 inhibition (100 mg sitagliptin/d, 8 wk): reduce circulating and adipose-specific markers of inflammation; and increase endothelial progenitor cell numbers used for vascular repair in 36 HIV+ adults with insulin resistance, central adiposity and CVD risk factors. The investigators hypothesize that sitagliptin will reduce circulating cytokine levels, reduce adipose tissue macrophage number and inflammation, and increase the number of circulating endothelial progenitor cells in HIV infected men and women. These physiological studies will advance our understanding about the efficacy of DPP4 inhibition in this high-risk group, and may help prevent the inexorable transition from insulin resistance to T2DM and CVD in HIV infected men and women.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sitagliptin | Experimental | Drug: Sitagliptin100 mg sitagliptin/day for 2 months |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo daily for 2 months |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 18-65 yr old HIV infected men and women.
- Stable (at least the past 6 months) on combined antiretroviral therapy (cART).
- Stable immune (> 300 CD4+ T-cells/µL) and virologic (< 50 copies HIV RNA/mL) status.
- Insulin resistant/impaired glucose tolerance (fasting glucose 100-125mg/dL, or 2-hr glucose 140-200mg/dL or fasting HOMA-IR= 2.5-6.0).
- Waist circumference > 102 cm (men), > 88 cm (women).
Key exclusion criteria (16 listed)
- Diabetes (T2DM, IDDM or diabetic ketoacidosis) or taking any glucose-lowering medication (e.g., insulin, TZDs, metformin, sulfonylurea).
- Any agent that might artifactually alter glycemic control (e.g., glucocorticoids, megace, rhGH, GH-secretagogue, testosterone derivatives, creatine monohydrate, chromium picolinate, AA/protein supplements, medium- or long-chain fatty acids) during 6 months prior to or during enrollment.
- History of serious CV disease. NYHA Functional Class III or IV (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, stroke, resting hypertension > 160/95 mmHg), irregular heart rhythm, resting ST-segment depression > 1mm). Treatment with medications for CV condition (e.g., α- or ß-blockers). Some BP-lowering medications (Ca++channel blocker, diuretic, or ACE inhibitor) are permitted.
- Moderate to severe renal insufficiency. Serum creatinine > 1.7 mg/dL (men) > 1.5 mg/dL (women).
- Plan or anticipate a change in anti-HIV medications during the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SitagliptinAlso: JanuviaOral, 100 mg/day for 2 months | Drug | Sitagliptin |
| Placebooral, matching placebo daily for 2 months | Drug | Placebo |
Primary outcome
Inflammatory Biomarker 1: Plasma hsCRP Concentration
Time frame: 2 months
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.
Inflammatory Biomarker 2: Plasma IL-6 Concentration
Time frame: 2 months
There are 3 levels of the primary outcome measure; hsCRP, IL-6, and D-dimer concentrations measured at baseline and week 8
Inflammatory Biomarker 3: Serum D-dimer Concentration
Time frame: 2 months
There are 3 levels of the primary outcome measure, hsCRP, IL-6, and D-dimer
2 secondary outcomes
Fold Change in Adipose Inflammation Marker CCL2 (MCP-1) mRNA Expression
Time frame: Baseline to 2 months
Percent Change in Blood Endothelial Progenitor Cells
Time frame: Baseline to 2 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25938633Best C, Struthers H, Laciny E, Royal M, Reeds DN, Yarasheski KE. Sitagliptin Reduces Inflammation and Chronic Immune Cell Activation in HIV+ Adults With Impaired Glucose Tolerance. J Clin Endocrinol Metab. 2015 Jul;100(7):2621-9. doi: 10.1210/jc.2015-1531. Epub 2015 May 4.
- Center for Clinical Studies- Washington UniversityLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin E Yarasheski, PhD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sitagliptin in people with Inflammation and Macrophage Infiltration, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Inflammatory Biomarker 1: Plasma hsCRP Concentration (time frame: 2 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01552694, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2018.