Sevelamer for Reducing Endotoxemia and Immune Activation
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
HIV-infected people can have an increase in inflammation in their body organs, even after taking anti-HIV medicines. Inflammation is a normal body reaction to any infection. However, if inflammation lasts a long time like in HIV infection, it may lead to complications, such as heart disease, cancer, liver disease, and problems with thinking. Also, HIV-infected people with high inflammation have lower CD4+ T-cell counts (cells that fight infection). Many HIV researchers are studying the harmful effects of this prolonged inflammation and possible ways to prevent these complications.
The increase in inflammation in HIV-infected people may be caused by HIV or by other factors such as parts of bacteria. These bacterial pieces, called endotoxins, do not cause harm in the intestine (gut). However, in HIV infection, there is damage to the gut that allows endotoxins to cross from the gut into the blood. These endotoxins then cause inflammation in the body. New research is focusing on strategies to reduce the levels of endotoxin as a way to decrease inflammation.
A drug called sevelamer carbonate is used to bind phosphate in dialysis patients. However, sevelamer carbonate also binds endotoxin in the gut and lowers endotoxin levels in the blood of dialysis patients. Sevelamer carbonate also decreases the inflammation endotoxin causes in dialysis patients. This study will see if sevelamer carbonate can have the same effects in HIV-infected patients.
The purpose of this study is to learn:
- How well sevelamer carbonate reduces bacterial components in the blood (endotoxemia).
- How well sevelamer carbonate reduces the level of activity of CD4+ and CD8+ T-cells in people infected with HIV.
- How safe sevelamer carbonate is in people infected with HIV.
Condition | Intervention | Phase |
---|---|---|
HIV-1 Infection |
Drug: Sevelamer carbonate |
Phase 2 |
Study Type: | Interventional |
Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
Official Title: | Sevelamer Carbonate for Reducing Endotoxemia and Immune Activation: A Proof of Concept Study |
- Change in soluble CD14 (sCD14) from week 0 to week 8 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
- Change in endotoxin from week 0 to week 8 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
- Change from baseline in CD4+ and CD8+ T-cell activation, defined as the %CD38+/HLA-DR+ and cycling, defined as %Ki67+ [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
- Change in levels of systemic inflammation (IL-6, CRP) from baseline. [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
- Change in sCD14 and endotoxin from baseline to week 4 and from week 8 to week 16. [ Time Frame: From baseline to week 4 & from week 8 to week 16 ] [ Designated as safety issue: No ]
- Change in blood phosphate levels from baseline. [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: Yes ]
- Change in levels of coagulation (d-dimer, tissue factor) from baseline. [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
- Change in plasma HIV-1 RNA levels [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
- Change in CD4+ T-cell counts [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
- Change in total cholesterol, LDL-cholesterol, HDL-cholesterol, and non-HDL cholesterol [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
- Change in fasting glucose [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
- Safety profile of sevelamer carbonate in HIV infected individuals, defined as Grade ≥ 2 signs and symptoms, Grade ≥ 2 laboratory abnormalities and other serious adverse events (SAEs) [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: Yes ]
Estimated Enrollment: | 40 |
Study Start Date: | November 2011 |
Estimated Study Completion Date: | November 2012 |
Estimated Primary Completion Date: | September 2012 (Final data collection date for primary outcome measure) |
-
Drug: Sevelamer carbonate
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- HIV-1 infection
- No plans to initiate ART during the course of the proposed study.
- Screening CD4+ T-cell count ≥ 400 cells/mm3 performed in a laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
- HIV-1 RNA >50 copies/mL within the last 180 days prior to entry.
- Screening serum phosphate > 2.6 mg/dL within 60 days prior to entry.
- Certain laboratory values, as detailed in section 4.1.6 of the protocol, obtained within 30 days prior to entry
- Female subjects of reproductive potential must have a negative serum or urine pregnancy test performed within 30 days prior to entry.
Female subjects participating in sexual activity that could lead to pregnancy must agree to use at least one of the following forms of birth control for at least 30 days prior to study entry until the final study visit:
- Condoms (male or female) with or without a spermicidal agent
- Diaphragm or cervical cap with spermicide
- Intrauterine device (IUD)
- Hormone-based contraceptive
- Female subjects who are not of reproductive potential are eligible without requiring the use of a contraceptive.
- Confirmation of the availability of the stored pre-entry plasma and peripheral blood mononuclear cell (PBMC) samples for endotoxin, sCD14, and immune activation determinations, obtained from a fasting sample.
- Ability and willingness of subject to provide informed consent.
- No plans to use probiotics (defined as products that contain significant amounts of live microorganisms and are ingested for specific health benefits, e.g., yogurt with live and active cultures, Lactobacillus GG, Saccharomyces boulardii) during the study.
Exclusion Criteria:
- Known diagnosis of acute HIV infection within 180 days prior to study entry.
- Pregnant or breastfeeding.
- Use of any antiretroviral agent within 24 weeks prior to study entry.
- Use of systemic cancer chemotherapy or radiation therapy, immunosuppressive or immunomodulatory therapy (e.g., interferons, tumor necrosis factor antagonists, interleukins, systemic corticosteroids) within 24 weeks prior to study entry.
NOTE A: Use of inhaled steroids, nasal steroids, topical steroids, or the equivalent of 10 mg of prednisone or less per day or a less than 2-week course of oral steroids is not exclusionary.
NOTE B: A single course of 1% hydrocortisone cream applied up to 3 times a day to <10 square inches area for <2 weeks is permitted while on study. Use of all other topical steroids is excluded.
- Known allergy/sensitivity or any hypersensitivity to components of the study drug or its formulation.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Serious illness requiring systemic treatment and/or hospitalization within 60 days prior to study entry.
- Known cirrhosis or severe liver disease (e.g., ascites, encephalopathy, history of variceal bleeding).
NOTE: Potential subjects with chronic hepatitis B or C virus infection who do not have known cirrhosis or severe liver disease may participate in the study.
- Severe kidney disease (defined as estimated glomerular filtration rate [GFR] <30 mL/min/1.73m2) at screening.
- History of bowel obstruction or severe GI motility disorders including severe constipation.
- Severe dysphagia or swallowing disorders.
- Major GI tract surgery within 60 days prior to study entry.
- Intent to initiate or change the dose of lipid-lowering drugs during study. NOTE: Potential subjects on stable doses of lipid-lowering agents (defined as no change in preparation or dose within 90 days prior to study entry) are permitted and may be enrolled.
- Use of investigational therapies within 90 days prior to study entry unless permission was granted by the A5296 protocol chairs (see Study Management page).
- Currently receiving hepatitis C therapy or anticipation that such therapy will be started during the study.
- Use of probiotics, for more than 3 consecutive days within the 60 days prior to study entry.
United States, Alabama | |
Alabama Therapeutics CRS (5801) | Recruiting |
Birmingham, Alabama, United States, 35294 | |
Contact: Karen Savage, BSN 205-975-7925 kgsavage@uab.edu | |
Principal Investigator: Victoria Johnson, MD | |
United States, California | |
UCLA CARE Center CRS (601) | Recruiting |
Los Angeles, California, United States, 90095 | |
Contact: Maricela Gonzalez 310-557-3798 mmgonzalez@mednet.ucla.edu | |
Principal Investigator: Judith Currier, MD, MSc | |
Stanford CRS (501) | Recruiting |
Palo Alto, California, United States, 94304 | |
Contact: Debbie Slamowitz, RN, BSN, ACRN (650) 723-2804 dslam@stanford.edu | |
Principal Investigator: Andrew Zolopa, MD | |
United States, Colorado | |
University of Colorado Hospital CRS (6101) | Recruiting |
Aurora, Colorado, United States, 80045 | |
Contact: Mary G Ray, RN, MSN 303-724-0712 graham.ray@uchsc.edu | |
Principal Investigator: Thomas B Campbell, MD | |
United States, Florida | |
Univ. of Miami AIDS CRS (901) | Recruiting |
Miami, Florida, United States, 33136 | |
Contact: Leslie Thompson, RN, BSN 305-243-3838 lthomps@gate.net | |
Principal Investigator: Margaret A. Fischl, MD | |
United States, Illinois | |
Northwestern University CRS (2701) | Recruiting |
Chicago, Illinois, United States, 60611 | |
Contact: Baiba Berzins, MPH 312-695-5012 baiba@northwestern.edu | |
Principal Investigator: Babafemi Taiwo, MBBS, MD | |
United States, Massachusetts | |
Brigham and Women's Hosp. ACTG CRS (107) | Recruiting |
Boston, Massachusetts, United States, 02115 | |
Contact: Jon Gothing, RN 617-732-5635 jgothing@partners.org | |
Principal Investigator: Paul E. Sax, MD | |
Massachusetts General Hospital ACTG CRS (101) | Recruiting |
Boston, Massachusetts, United States, 02114 | |
Contact: Teri Flynn, RN, ANP, MSN 617-724-0072 tflynn@partners.org | |
Principal Investigator: Rajesh Gandhi, MD | |
United States, Missouri | |
Washington University CRS (2101) | Recruiting |
St. Louis, Missouri, United States, 63110 | |
Contact: Michael Klebert, RNC, PhD, ANP 1-314-747-1098 mklebert@im.wustl.edu | |
Principal Investigator: Jessica R. Grubb, MD | |
United States, New York | |
AIDS Care CRS (1108) | Recruiting |
Rochester, New York, United States, 14642 | |
Contact: Carol Greisberger, RN, BS 585-275-2740 carol_greisberger@urmc.rochester.edu | |
Principal Investigator: Roberto Corales, DO, AAHIVS | |
Univ. of Rochester ACTG CRS (1101) | Recruiting |
Rochester, New York, United States, 14642 | |
Contact: Carol Greisberger, RN, BS 585-275-2740 carol_greisberger@urmc.rochester.edu | |
Principal Investigator: Amneris Luque, MD | |
United States, Ohio | |
Univ. of Cincinnati CRS (2401) | Recruiting |
Cincinnati, Ohio, United States, 45267 | |
Contact: Tammy Mansfield, RN 513-584-8373 mansfitl@ucmail.uc.edu | |
Principal Investigator: Judith Feinberg, MD | |
Case CRS (2501) | Recruiting |
Cleveland, Ohio, United States, 44106 | |
Contact: Jane Baum, BSN, RN 216-844-2546 baum.jane@clevelandactu.org | |
Principal Investigator: Michael Lederman, MD | |
Metro Health CRS (2503) | Recruiting |
Cleveland, Ohio, United States, 44109 | |
Contact: Julie Ziegler 216-778-7847 jziegler@metrohealth.org | |
Principal Investigator: Robert C. Kalayjian, MD | |
United States, Pennsylvania | |
Hosp. of the Univ. of Pennsylvania CRS (6201) | Recruiting |
Philadelphia, Pennsylvania, United States, 19104 | |
Contact: Joseph Quinn, RN 215-349-8091 joseph.quinn@uphs.upenn.edu | |
Principal Investigator: Pablo Tebas, MD | |
Pittsburgh CRS (1001) | Recruiting |
Pittsburgh, Pennsylvania, United States, 15213 | |
Contact: Christine Tripoli, BSN, RN 412-647-0771 tripolica@upmc.edu | |
Principal Investigator: Sharon Riddler, MD, MPH | |
United States, Texas | |
Houston AIDS Research Team CRS (31473) | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Hilda Cuervo, BS 713-500-6751 Hilda.Cuervo@uth.tmc.edu | |
Principal Investigator: Roberto Arduino, MD | |
United States, Washington | |
University of Washington AIDS CRS (1401) | Recruiting |
Seattle, Washington, United States, 98104 | |
Contact: Christine Jonsson 206-744-8886 cjonsson@uw.edu | |
Principal Investigator: Ann Collier, MD |
Study Chair: | Rajesh Gandhi, MD | Massachusetts General Hospital ACTG CRS |
Study Chair: | Netanya Sandler, MD | National Institutes of Health (NIH) |
No publications provided
Responsible Party: | AIDS Clinical Trials Group |
ClinicalTrials.gov Identifier: | NCT01543958 History of Changes |
Other Study ID Numbers: | ACTG A5296, 1U01AI068636 |
Study First Received: | February 29, 2012 |
Last Updated: | February 29, 2012 |
Health Authority: | United States: Federal Government |
Additional relevant MeSH terms:
Endotoxemia HIV Infections Bacteremia Sepsis Infection Toxemia Systemic Inflammatory Response Syndrome Inflammation Pathologic Processes Lentivirus Infections Retroviridae Infections |
RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Sevelamer Chelating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
ClinicalTrials.gov processed this record on October 17, 2012