HIVPhase 2NCT00864916
Pentoxifylline and Combination Antiretroviral Therapy to Improve Blood Vessel Function in HIV-Infected People
A Phase 2 study testing Combination antiretroviral therapy (cART) and Pentoxifylline in people with HIV and Vascular Diseases, run by Indiana University at 1 site in United States.
Trial summary
People infected with HIV have a greater risk of developing cardiovascular disease than people not infected with HIV. This may be due to increased inflammation in the blood vessels. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV, Vascular Diseases, Cardiovascular Diseases
- What is being tested?
- Combination antiretroviral therapy (cART) and Pentoxifylline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to Dec 2012
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documentation of HIV infection with a positive HIV enzyme-linked immunosorbent assay (ELISA) test and confirmatory western blot test
- Has not received any antiretroviral therapies in the 6 months before screening
- Participant is planning to initiate cART, per the primary HIV caregiver (there is no CD4 or HIV-1 RNA level criteria)
Who cannot join
- Incarceration at the time of screening or at any study visit
- Diagnosed vascular disease, including history of angina pectoris, coronary disease, peripheral vascular disease, cerebrovascular disease, aortic aneurysm, or otherwise known atherosclerotic disease
- Diagnosed disease or process, other than HIV infection, associated with increased systemic inflammation (including, but not limited to, systemic lupus erythematosis, inflammatory bowel diseases, or other collagen vascular diseases). Hepatitis B or C co-infections are NOT exclusionary.
- History of bleeding diathesis, gastrointestinal ulceration or bleeding, cerebrovascular aneurysm or bleeding, or retinal hemorrhage
- Known or suspected cancer requiring systemic treatment in the 6 months before screening
- History of American Diabetes Association (ADA)-defined diabetes mellitus. History of gestational diabetes is not exclusionary.
Show all 31Show fewer
- History of migraine headaches
- History of Raynaud's phenomenon
- History of cardiac arrhythmias or cardiomyopathy
- History of hypothyroidism or hyperthyroidism, even if treated
- Known allergy or intolerance to pentoxifylline or other methylxanthines (e.g., theophylline, caffeine, theobromine). Use of caffeinated products, except on the mornings of the study visits, is not exclusionary.
- Known allergy or intolerance to nitroglycerin
- History of carotid bruits
- Creatinine clearance less than 50 mL/min, using the Cockcroft-Gault equation and a serum creatinine level measured in the 28 days before screening or at the screening visit
- Hemoglobin less than 9.0 mg/dL in the 28 days before screening or at the screening visit
- Alanine aminotransferase (ALT) level or aspartate aminotransferase (AST) greater than three times the upper limit of normal (ULN) in the 28 days before screening or at the screening visit
- Total bilirubin greater than 2.5 times ULN in the 28 days before screening or at the screening visit
- Fever, defined as a temperature greater than or equal to 38.0 degrees Celsius (C) in the 48 hours before screening. Fever in the 48 hours before each study visit will require postponement of that study visit until the participant's temperature has been lower than 38.0 C for at least 48 hours; fevers continuing past the allowed study visit timeframe will result in study discontinuation.
- Therapy for acute infection or other serious medical illnesses (besides HIV infection) within 14 days prior to screening.
- Note: Therapy for acute infection or other serious medical illnesses that overlaps with a main study visit will result in postponement of that study visit until the course of therapy is completed; postponement outside of the allowed study visit timeframe will result in study discontinuation.
- Pregnancy or breastfeeding during the course of the study.
- Hypotension, defined as systolic blood pressure < 90mmHg, at time of screening.
- Note: Hypotension noted prior to brachial artery reactivity testing on each main study visit will result in study visit postponement of at least one day until systolic pressure is ≥ 90mmHg the morning of brachial reactivity testing; postponement outside of the allowed study visit timeframe will result in study discontinuation.
- Uncontrolled hypertension, defined as a confirmed systolic blood pressure > 160mmHg at screening (regardless of use of antihypertensive medications).
- Receipt of anti-inflammatory agents (including, but not limited to, plaquenil, infliximab, etanercept, mycophenylate mofetil, sirolimus, tacrolimus, cyclosporine, pentoxifylline, thalidomide).
- Receipt of investigational agents, cytotoxic chemotherapy, systemic or topical glucocorticoids (of any dose), or anabolic steroids within 28 days of screening.
- Note: Physiologic testosterone replacement therapy is not exclusionary.
- Receipt of lipid-lowering drugs, acetazolamide, anticoagulants, anticonvulsants, or thyroid replacements within 28 days prior to screening.
- Receipt of aspirin or other NSAIDS within 7 days of screening.
- Use of sildenafil, vardenafil, or tadalafil within 72 hours (before or after) of each main study visit.
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
Infectious Diseases Research Center
Indianapolis, Indiana, 46202
About this study
Official title: A Randomized, Placebo-Controlled Trial of Pentoxifylline Plus Combination ART vs. Combination ART Alone to Improve Endothelial Dysfunction in HIV-Infected Patients
People infected with HIV have a greater risk of developing cardiovascular disease than people not infected with HIV. This may be due to increased inflammation in the blood vessels. This study will determine whether an anti-inflammatory drug, pentoxifylline, in combination with antiretroviral medications, is more effective at improving blood vessel function and reducing inflammation than antiretroviral medications alone in people infected with HIV.
Read the detailed description
People infected with HIV have an increased risk for cardiovascular disease, which is a leading cause of death for those with HIV. This may be due to increased inflammation of the blood vessels, which is often observed in HIV-infected people and which can lead to endothelial dysfunction-a condition that involves the malfunctioning of the thin layer of cells that line the interior surface of blood vessels. Endothelial dysfunction increases the risk of developing both atherosclerosis and cardiovascular disease.
Much of the focus on the causes of HIV-related endothelial dysfunction has been centered on the use of several types of antiretroviral medications used to treat HIV infection. However, more recent data suggest that newer protease inhibitors, a type of antiretroviral medication, are not associated with endothelial dysfunction and that newer combination antiretroviral therapy (cART) regimens result in an initial improvement in endothelial dysfunction. Yet, preliminary research has also shown that in people who receive cART, the risk of endothelial dysfunction in fact persists with time, suggesting that a mechanism other than viral control, notably inflammation, is playing a role in endothelial dysfunction. Pentoxifylline is a medication that is currently used to reduce leg pain in people with blockages in the blood vessels in their legs. Previous research has shown that pentoxifylline may improve blood vessel function and reduce inflammation in people infected with HIV, but more research is needed to confirm these benefits. The purpose of this study is to compare the safety and effectiveness of pentoxifylline and cART versus cART alone at improving endothelial function and reducing inflammation in HIV-infected people.
This study will enroll people infected with HIV who are about to start receiving cART. At a baseline study visit, participants will undergo a medical history review; physical examination; measurements of blood pressure, heart rate, height, weight, temperature, waist, and hip; and blood and urine collection. An ultrasound imaging test of the arm will measure blood vessel function. Participants will then be randomly assigned to receive either pentoxifylline or placebo three times a day for 48 weeks. All participants will also receive cART medications, as prescribed by their primary HIV doctor. At study visits at Weeks 4, 8, 16, 24, 32, and 48, participants will undergo repeat baseline measurements; however, the ultrasound testing will only occur at Weeks 8, 24, and 48.
- Conditions
- HIV, Vascular Diseases, Cardiovascular Diseases, Atherosclerosis, HIV Infections
- Being tested
- Combination antiretroviral therapy (cART), Pentoxifylline, Placebo
- Keywords
- Endothelial Function, Pentoxifylline, Antiretroviral Therapy, Inflammation
- Medical subject headings
- Vascular Diseases, Cardiovascular Diseases, Atherosclerosis, HIV Infections, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination antiretroviral therapy (cART)Drug
Participants will receive the appropriate cART medications, as prescribed by their primary HIV doctor for 48 weeks. (cART medications may be prescribed beyond the length of this study.)
PentoxifyllineDrug
Participants will receive 400 mg of pentoxifylline three times per day for 48 weeks.
PlaceboDrug
Participants will receive placebo three times per day for 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive pentoxifylline and combination antiretroviral therapy (cART). Receives: Drug: Combination antiretroviral therapy (cART); Drug: Pentoxifylline |
| 2 | Active comparator | Participants will receive placebo and cART. Receives: Drug: Combination antiretroviral therapy (cART); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Flow-mediated Dilation of the Brachial Artery
Flow-mediated dilation (% dilation of the brachial artery) at week 48
Measured: Measured at Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2009 (estimated)
- Study startMar 2009
- Primary completionDec 2012
- Study completionDec 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.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Samir K Gupta, MD, MS, Indiana University
- Investigators
- Samir K. Gupta, MD, MS, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00864916
- Sponsor's protocol ID
- 646
- Other IDs
- R01HL095149
- Status last verified
- Apr 2014
- First submitted
- 17 Mar 2009
- Last updated
- 12 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-Controlled Trial of Pentoxifylline Plus Combination ART vs. Combination ART Alone to Improve Endothelial Dysfunction in HIV-Infected Patients
- ClinicalTrials.gov ID
- NCT00864916
- Acronym / sponsor ID
- 646
- Conditions
- HIV, Vascular Diseases, Cardiovascular Diseases, Atherosclerosis, HIV Infections
- Keywords
- Endothelial Function, Pentoxifylline, Antiretroviral Therapy, Inflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2009
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 19 Mar 2009 (estimated)
- Results
- Posted 16 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
People infected with HIV have a greater risk of developing cardiovascular disease than people not infected with HIV. This may be due to increased inflammation in the blood vessels. This study will determine whether an anti-inflammatory drug, pentoxifylline, in combination with antiretroviral medications, is more effective at improving blood vessel function and reducing inflammation than antiretroviral medications alone in people infected with HIV.
Detailed description
People infected with HIV have an increased risk for cardiovascular disease, which is a leading cause of death for those with HIV. This may be due to increased inflammation of the blood vessels, which is often observed in HIV-infected people and which can lead to endothelial dysfunction-a condition that involves the malfunctioning of the thin layer of cells that line the interior surface of blood vessels. Endothelial dysfunction increases the risk of developing both atherosclerosis and cardiovascular disease.
Much of the focus on the causes of HIV-related endothelial dysfunction has been centered on the use of several types of antiretroviral medications used to treat HIV infection. However, more recent data suggest that newer protease inhibitors, a type of antiretroviral medication, are not associated with endothelial dysfunction and that newer combination antiretroviral therapy (cART) regimens result in an initial improvement in endothelial dysfunction. Yet, preliminary research has also shown that in people who receive cART, the risk of endothelial dysfunction in fact persists with time, suggesting that a mechanism other than viral control, notably inflammation, is playing a role in endothelial dysfunction. Pentoxifylline is a medication that is currently used to reduce leg pain in people with blockages in the blood vessels in their legs. Previous research has shown that pentoxifylline may improve blood vessel function and reduce inflammation in people infected with HIV, but more research is needed to confirm these benefits. The purpose of this study is to compare the safety and effectiveness of pentoxifylline and cART versus cART alone at improving endothelial function and reducing inflammation in HIV-infected people.
This study will enroll people infected with HIV who are about to start receiving cART. At a baseline study visit, participants will undergo a medical history review; physical examination; measurements of blood pressure, heart rate, height, weight, temperature, waist, and hip; and blood and urine collection. An ultrasound imaging test of the arm will measure blood vessel function. Participants will then be randomly assigned to receive either pentoxifylline or placebo three times a day for 48 weeks. All participants will also receive cART medications, as prescribed by their primary HIV doctor. At study visits at Weeks 4, 8, 16, 24, 32, and 48, participants will undergo repeat baseline measurements; however, the ultrasound testing will only occur at Weeks 8, 24, and 48.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Combination antiretroviral therapy (cART), Drug: PentoxifyllineParticipants will receive pentoxifylline and combination antiretroviral therapy (cART). |
| 2 | Active comparator | Drug: Combination antiretroviral therapy (cART), Drug: PlaceboParticipants will receive placebo and cART. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Documentation of HIV infection with a positive HIV enzyme-linked immunosorbent assay (ELISA) test and confirmatory western blot test
- Has not received any antiretroviral therapies in the 6 months before screening
- Participant is planning to initiate cART, per the primary HIV caregiver (there is no CD4 or HIV-1 RNA level criteria)
Key exclusion criteria (31 listed)
- Incarceration at the time of screening or at any study visit
- Diagnosed vascular disease, including history of angina pectoris, coronary disease, peripheral vascular disease, cerebrovascular disease, aortic aneurysm, or otherwise known atherosclerotic disease
- Diagnosed disease or process, other than HIV infection, associated with increased systemic inflammation (including, but not limited to, systemic lupus erythematosis, inflammatory bowel diseases, or other collagen vascular diseases). Hepatitis B or C co-infections are NOT exclusionary.
- History of bleeding diathesis, gastrointestinal ulceration or bleeding, cerebrovascular aneurysm or bleeding, or retinal hemorrhage
- Known or suspected cancer requiring systemic treatment in the 6 months before screening
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 |
|---|---|---|
| Combination antiretroviral therapy (cART)Participants will receive the appropriate cART medications, as prescribed by their primary HIV doctor for 48 weeks. (cART medications may be prescribed beyond the length of this study.) | Drug | 1, 2 |
| PentoxifyllineParticipants will receive 400 mg of pentoxifylline three times per day for 48 weeks. | Drug | 1 |
| PlaceboParticipants will receive placebo three times per day for 48 weeks. | Drug | 2 |
Primary outcome
Flow-mediated Dilation of the Brachial Artery
Time frame: Measured at Week 48
Flow-mediated dilation (% dilation of the brachial artery) at week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for HIV
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
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.
Samir K. Gupta, MD, MS principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Combination antiretroviral therapy (cART) and Pentoxifylline in people with HIV and Vascular Diseases, run by Indiana University 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 3 inclusion and 31 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 12 May 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 Apr 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?
Flow-mediated Dilation of the Brachial Artery (time frame: Measured at Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 May 2014.