DiabetesPhase 2/3DPPIVinHIVNCT01093651
Dipeptidyl Peptidase-4 Inhibition and Immune Function in HIV
A Phase 2/3 study testing Sitagliptin in people with Diabetes and Insulin Resistance, run by Washington University School of Medicine at 1 site in United States.
Trial summary
We will test the safety of a new class of anti-diabetes compounds (DPPIV-inhibitors) in people living with HIV. Future trials will examine efficacy for treating diabetes and reducing cardiovascular disease risk in people living with HIV. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetes, Insulin Resistance
- What is being tested?
- Sitagliptin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to Jun 2012
- Phase
- Phase 2/3
- 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
- Thirty 18-65 yr old HIV-infected men and women (with source documentation of HIV status) who are stable on any antiretroviral therapy (cART) regimen
- Have stable (at least the past 12-months) immunologic (>350 CD4+ T-cells/µL) and virologic (<50 copies HIV RNA/mL) status.
- BMI 18-42kg/m2;
- Normal blood chemistry for at least 1 month prior to enrollment;
- Platelet count > 30,000/mm3, absolute neutrophil count >750/mm3, transaminases < 2.5x the upper limit of normal (ULN).
- Long-term non-progressors (not on ART) are not eligible.
Who cannot join
- CD4+ T-cell count <350 cells/µL or detectable plasma HIV RNA (>50 copies HIV RNA/mL) within the past 12-months. During the study, if CD4+ T-cell count declines by >100 cells/µL, or if plasma HIV RNA becomes detectable (>50 copies HIV RNA/mL after repeat analysis 2wks apart), and the participant denies any lapse in their anti-HIV medication regimen, the study medication will be stopped and an adverse event documented. If at any time during the study, two participants experience a reduction in T-cell count >100 cells/µL, or their plasma HIV RNA levels become detectable (>50 copies HIV RNA/mL after repeat analysis 2wks apart), and they are confirmed (by unblinding) to have received sitagliptin, the study will be stopped for serious safety concerns.
- Systemic, secondary or opportunistic infection within past 12-months.
- Fasting glucose intolerance (FBG >100mg/dL), fasting hyperinsulinemia (>15µU/mL), or fasting insulin resistance (Homeostasis model for insulin resistance (HOMA) >3.0). Any agents that might alter glucose metabolism (insulin, TZDs, metformin, glucocorticoids, sulfonylurea, corticosteroids, megace, rhGH, GH-secretagogue) during the 3 months prior to enrollment or at any time during enrollment. Volunteers with T2DM, IDDM or diabetic ketoacidosis will not be enrolled.
- History of serious CV disease or NYHA Functional Class III or IV, (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, valve disease (murmur), stroke, uncontrolled high blood pressure (resting >160/95 mmHg), irregular heart rhythm, resting ST-segment depression >1mm). Treatment with medications for a CV condition (cardiac glycosides α- or ß-blockers). Some antihypertensive medications (calcium-channel blocker, diuretic, angiotensin II receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACE)) will be permitted.
- Moderate to severe renal insufficiency. Serum creatinine >1.7 mg/dL (men) >1.5 mg/dL (women).
- Known allergy or hypersensitivity to DPPIV-inhibitors.
Show all 19Show fewer
- Plan to change anti-HIV medication regimen or prophylaxis for opportunistic infection within 6-months of starting study.Transitions among efavirenz-based regimens will be allowed (e.g., Efavirenz + lamivudine + zidovudine (combivir) to Efavirenz + emtricitabine + tenofovir (Atripla)).
- Lipid-lowering medications are permitted (fibrate or statin or niacin), but must be stable on that agent for at least 3 months prior to enrollment. Lipid-lowering agents cannot be started during the treatment period.
- Chronic hepatitis B infection (HB surface antigen positive). Active hepatitis C infection (detectable Hep C RNA). Those who have cleared hepatitis B or C infection are eligible.
- Hematocrit <34% in men or <25% in women with symptoms (fatigue, "tired-legs", shortness of breath). Hemoglobin <10 gm/100ml with symptoms.
- Nausea, vomiting, diarrhea (>4 loose stools/day) that are unresponsive to treatment. History of eating disorder or significant GI-disease.
- Pregnant or nursing mothers. Women must agree to use an acceptable form of birth control during the study. If birth control pills are used, the woman must be stable on these medications for at least 6 months prior to enrollment.
- Active malignancy or treatment with chemotherapeutic agents or radiation therapy (within past 12 months).
- >10% unintentional body weight loss during the 12 months prior to enrollment.
- "Blinded" investigational drugs/medications during the 3 months prior to enrollment that will not be unblinded before enrollment. Open-label investigational drugs are permitted (within past 3 months, no plan to stop during enrollment and not known to affect glucose, lipid, adipose tissue or liver metabolism).
- Over the counter agents that might alter glucose, lipid, or adipose tissue metabolism (e.g., creatine monohydrate, chromium picolinate, amino acid/protein supplements, medium- or long-chain fatty acids) within 1 month of enrollment. These supplements are not permitted during the treatment period.
- Reduced cognitive function/unable to provide voluntary informed consent. Prisoners are excluded.
- Active substance abuse that the physician-scientist believes may compromise safety, compliance, or interfere with study drug or data interpretation.
- Any cytokine or anti-cytokine therapy during 3 months prior to enrollment.
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 Blinded Randomized Controlled Pilot Immunologic and Virologic Safety Trial of an FDA-approved DPPIV-inhibitor in HIV+ Men and Women
We will test the safety of a new class of anti-diabetes compounds (DPPIV-inhibitors) in people living with HIV. Future trials will examine efficacy for treating diabetes and reducing cardiovascular disease risk in people living with HIV.
Read the detailed description
Human immunodeficiency virus (HIV)-infection and treatment with antiretroviral therapies are associated with several cardiometabolic risk factors; insulin resistance, diabetes, dyslipidemia, central adiposity, that increase risk for MI and stroke. A new class of drugs used to treat type 2 diabetes has been introduced; Dipeptidyl peptidase-IV (DPPIV)-inhibitors (Januvia®, Onglyza®, alogliptin). Dipeptidyl peptidase-IV (DPPIV)-inhibition could be a safe and effective therapy for HIV-associated insulin resistance and diabetes. However, no safety data exist. The research question is: If HIV+ adults with stable immunologic (CD4+ T-cell count >350 cells/μL) and virologic (plasma HIV RNA <50 copies/mL) function are given a DPPIV-inhibitor would their CD4+ T-cell count and plasma HIV RNA level increase, decrease, or stay the same? Theoretically, DPPIV-inhibition could enhance their immune system by increasing SDF-1α levels; a potent inhibitor of HIV-entry into T-cells, or harm the HIV+ immune system by inactivating CD26 on immune cells. We hypothesize that DPPIV-inhibition will not harm the immune system in HIV+ people. We propose a blinded randomized controlled pilot safety trial of an FDA-approved DPPIV-inhibitor in virologically- and immunologically-stable HIV+ men and women. We will monitor CD4+ T-cell count, plasma HIV RNA levels, immune activation markers, and safety outcomes (lipid/lipoprotein profiles, blood pressure, kidney and liver function) during 4-6 months of DPPIV-inhibitor exposure vs placebo in 20 HIV+ adults. If safety is confirmed, the efficacy of DPPIV-inhibition in HIV+ with insulin resistance will be tested in future trials that examine potential glucoregulatory and cardiovascular benefits.
- Conditions
- Diabetes, Insulin Resistance
- Being tested
- Sitagliptin, Placebo
- Medical subject headings
- Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitagliptinDrug
100 mg sitagliptin daily for 4-6 months
PlaceboDrug
Daily placebo for 4-6 months
| Study group | Role | What they receive |
|---|---|---|
| DPPIV inhibition | Experimental | Four to six months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Receives: Drug: Sitagliptin |
| Placebo | Placebo comparator | Four to six months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
CD4+ T-cell Count
Measured: Monthly for 4 months
Plasma HIV Viremia (Viral Load)
Percentage of participants with plasma HIV RNA copy number less than 48 copies/mL
Measured: Monthly for 6 months
Secondary outcomes (5)
Soluble TNFR2; Serum Biomarkers of Immune Activation
serum soluble tumor necrosis factor receptor-2 concentration
Measured: Baseline, week 8, week 16
SDF1α; Serum Biomarkers of Immune Activation
serum stromal cell-derived factor-1α concentration
Measured: Baseline, week 8, week 16
RANTES; Serum Biomarkers of Immune Activation
serum Regulated on Activation, Normal T cell Expressed and Secreted concentration
Measured: Baseline, week 8, week 16
Oral Glucose Tolerance
Area under the 75-gr oral glucose tolerance curve (AUCg) based on plasma glucose values measured at 0, 30, 60, 90, and 120 mins post-glucose challenge.
Measured: Baseline, week 8, week 16
Self-reported Symptoms
Cumulative number of self-reported symptoms based on the Division of AIDS Grading Scale for the Severity of Adult Adverse Events (0-4 scale where 0 is no new symptoms, 4 is serious adverse event or toxicity)
Measured: Monthly for 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2010 (estimated)
- Study startJun 2010
- Primary completionJun 2011
- Study completionJun 2012
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 DiabetesStudies 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 2/3
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Campbell Foundation
- 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
- NCT01093651
- Sponsor's protocol ID
- KEY03222010
- Acronym
- DPPIVinHIV
- Status last verified
- Jan 2014
- First submitted
- 23 Mar 2010
- Last updated
- 17 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Goodwin SR, Reeds DN, Royal M, Struthers H, Laciny E, Yarasheski KE. Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study. J Clin Endocrinol Metab. 2013 Feb;98(2):743-51. doi: 10.1210/jc.2012-3532. Epub 2012 Dec 21.
PubMed 23264399
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Blinded Randomized Controlled Pilot Immunologic and Virologic Safety Trial of an FDA-approved DPPIV-inhibitor in HIV+ Men and Women
- ClinicalTrials.gov ID
- NCT01093651
- Acronym / sponsor ID
- DPPIVinHIV / KEY03222010
- Conditions
- Diabetes, Insulin Resistance
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- The Campbell Foundation
- Study start
- Jun 2010
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 26 Mar 2010 (estimated)
- Results
- Posted 23 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We will test the safety of a new class of anti-diabetes compounds (DPPIV-inhibitors) in people living with HIV. Future trials will examine efficacy for treating diabetes and reducing cardiovascular disease risk in people living with HIV.
Detailed description
Human immunodeficiency virus (HIV)-infection and treatment with antiretroviral therapies are associated with several cardiometabolic risk factors; insulin resistance, diabetes, dyslipidemia, central adiposity, that increase risk for MI and stroke. A new class of drugs used to treat type 2 diabetes has been introduced; Dipeptidyl peptidase-IV (DPPIV)-inhibitors (Januvia®, Onglyza®, alogliptin). Dipeptidyl peptidase-IV (DPPIV)-inhibition could be a safe and effective therapy for HIV-associated insulin resistance and diabetes. However, no safety data exist. The research question is: If HIV+ adults with stable immunologic (CD4+ T-cell count >350 cells/μL) and virologic (plasma HIV RNA <50 copies/mL) function are given a DPPIV-inhibitor would their CD4+ T-cell count and plasma HIV RNA level increase, decrease, or stay the same? Theoretically, DPPIV-inhibition could enhance their immune system by increasing SDF-1α levels; a potent inhibitor of HIV-entry into T-cells, or harm the HIV+ immune system by inactivating CD26 on immune cells. We hypothesize that DPPIV-inhibition will not harm the immune system in HIV+ people. We propose a blinded randomized controlled pilot safety trial of an FDA-approved DPPIV-inhibitor in virologically- and immunologically-stable HIV+ men and women. We will monitor CD4+ T-cell count, plasma HIV RNA levels, immune activation markers, and safety outcomes (lipid/lipoprotein profiles, blood pressure, kidney and liver function) during 4-6 months of DPPIV-inhibitor exposure vs placebo in 20 HIV+ adults. If safety is confirmed, the efficacy of DPPIV-inhibition in HIV+ with insulin resistance will be tested in future trials that examine potential glucoregulatory and cardiovascular benefits.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DPPIV inhibition | Experimental | Drug: SitagliptinFour to six months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. |
| Placebo | Placebo comparator | Drug: PlaceboFour to six months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Thirty 18-65 yr old HIV-infected men and women (with source documentation of HIV status) who are stable on any antiretroviral therapy (cART) regimen
- Have stable (at least the past 12-months) immunologic (>350 CD4+ T-cells/µL) and virologic (<50 copies HIV RNA/mL) status.
- BMI 18-42kg/m2;
- Normal blood chemistry for at least 1 month prior to enrollment;
- Platelet count > 30,000/mm3, absolute neutrophil count >750/mm3, transaminases < 2.5x the upper limit of normal (ULN).
Key exclusion criteria (19 listed)
- CD4+ T-cell count <350 cells/µL or detectable plasma HIV RNA (>50 copies HIV RNA/mL) within the past 12-months. During the study, if CD4+ T-cell count declines by >100 cells/µL, or if plasma HIV RNA becomes detectable (>50 copies HIV RNA/mL after repeat analysis 2wks apart), and the participant denies any lapse in their anti-HIV medication regimen, the study medication will be stopped and an adverse event documented. If at any time during the study, two participants experience a reduction in T-cell count >100 cells/µL, or their plasma HIV RNA levels become detectable (>50 copies HIV RNA/mL after repeat analysis 2wks apart), and they are confirmed (by unblinding) to have received sitagliptin, the study will be stopped for serious safety concerns.
- Systemic, secondary or opportunistic infection within past 12-months.
- Fasting glucose intolerance (FBG >100mg/dL), fasting hyperinsulinemia (>15µU/mL), or fasting insulin resistance (Homeostasis model for insulin resistance (HOMA) >3.0). Any agents that might alter glucose metabolism (insulin, TZDs, metformin, glucocorticoids, sulfonylurea, corticosteroids, megace, rhGH, GH-secretagogue) during the 3 months prior to enrollment or at any time during enrollment. Volunteers with T2DM, IDDM or diabetic ketoacidosis will not be enrolled.
- History of serious CV disease or NYHA Functional Class III or IV, (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, valve disease (murmur), stroke, uncontrolled high blood pressure (resting >160/95 mmHg), irregular heart rhythm, resting ST-segment depression >1mm). Treatment with medications for a CV condition (cardiac glycosides α- or ß-blockers). Some antihypertensive medications (calcium-channel blocker, diuretic, angiotensin II receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACE)) will be permitted.
- Moderate to severe renal insufficiency. Serum creatinine >1.7 mg/dL (men) >1.5 mg/dL (women).
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 |
|---|---|---|
| Sitagliptin100 mg sitagliptin daily for 4-6 months | Drug | DPPIV inhibition |
| PlaceboDaily placebo for 4-6 months | Drug | Placebo |
Primary outcome
CD4+ T-cell Count
Time frame: Monthly for 4 months
Plasma HIV Viremia (Viral Load)
Time frame: Monthly for 6 months
Percentage of participants with plasma HIV RNA copy number less than 48 copies/mL
5 secondary outcomes
Soluble TNFR2; Serum Biomarkers of Immune Activation
Time frame: Baseline, week 8, week 16
SDF1α; Serum Biomarkers of Immune Activation
Time frame: Baseline, week 8, week 16
RANTES; Serum Biomarkers of Immune Activation
Time frame: Baseline, week 8, week 16
Oral Glucose Tolerance
Time frame: Baseline, week 8, week 16
Self-reported Symptoms
Time frame: Monthly for 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23264399Goodwin SR, Reeds DN, Royal M, Struthers H, Laciny E, Yarasheski KE. Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study. J Clin Endocrinol Metab. 2013 Feb;98(2):743-51. doi: 10.1210/jc.2012-3532. Epub 2012 Dec 21.
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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 2/3 study testing Sitagliptin in people with Diabetes and Insulin Resistance, 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 6 inclusion and 19 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 17 Feb 2014. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 23 Jan 2014). 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?
CD4+ T-cell Count (time frame: Monthly for 4 months). The study lists 2 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 NCT01093651, 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 17 Feb 2014.