Sevelamer for Reducing Endotoxemia and Immune Activation

NCT01543958 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A52961U01AI068636
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 15

Brief Summary

HIV-infected people can have an increase in inflammation in their body organs, even after taking anti-HIV medicines. Sevelamer carbonate is used to bind phosphate in dialysis patients. It can also bind endotoxin in the gut and lowers endotoxin levels in the blood of dialysis patients. Sevelamer carbonate decreases the inflammation endotoxin causes in dialysis patients. A5296 is a phase II, single-arm study to evaluate the effect of 8 weeks of sevelamer carbonate administration on markers of microbial translocation and T-cell activation in the blood in chronically HIV-infected subjects not receiving ART.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (2)

• Change in Endotoxin

  Change in LPS from baseline to week 8, where baseline value is the average of pre-entry and entry values.

  baseline and Week 8

• Change in Soluble CD14 (sCD14)

  Change in soluble CD14 (sCD14) from baseline to week 8, where baseline value is the average of pre-entry and entry

  baseline and week 8

Secondary Outcomes (48)

• Change in Endotoxin

  baseline and week 4

• Change in Endotoxin

  week 8 and week 16

• Change in sCD14

  baseline and week 4

• Change in sCD14

  week 8 and week 16

• Change in CD4+ T-cell Activation

  baseline and week 8

Study Arms (1)

Sevelamer carbonate

EXPERIMENTAL

Patients will be administered two 800 mg tablets of Sevelamer carbonate orally three times a day for 8 weeks.

Drug: Sevelamer carbonate; Device: Sevelamer carbonate

Interventions

Sevelamer carbonate DRUG

Patients will be administered two 800 mg tablets of Sevelamer carbonate orally three times a day for 8 weeks.

Also known as: Renvela

Sevelamer carbonate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (15)

Alabama Therapeutics CRS (5801)

Birmingham, Alabama, 35294, United States

Location

UCLA CARE Center CRS (601)

Los Angeles, California, 90095, United States

Location

Ucsf Aids Crs (801)

San Francisco, California, 94110, United States

Location

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Univ. of Miami AIDS CRS (901)

Miami, Florida, 33136, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, 02114, United States

Location

Washington University CRS (2101)

St Louis, Missouri, 63110, United States

Location

AIDS Care CRS (1108)

Rochester, New York, 14642, United States

Location

Univ. of Rochester ACTG CRS (1101)

Rochester, New York, 14642, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

Metro Health CRS (2503)

Cleveland, Ohio, 44109, United States

Location

Hosp. of the Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Sandler NG, Zhang X, Bosch RJ, Funderburg NT, Choi AI, Robinson JK, Fine DM, Coombs RW, Jacobson JM, Landay AL, Douek DC, Tressler R, Read SW, Wilson CC, Deeks SG, Lederman MM, Gandhi RT; AIDS Clinical Trials Group A5296 Team. Sevelamer does not decrease lipopolysaccharide or soluble CD14 levels but decreases soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol levels in individuals with untreated HIV infection. J Infect Dis. 2014 Nov 15;210(10):1549-54. doi: 10.1093/infdis/jiu305. Epub 2014 May 26.

  PMID: 24864123 DERIVED

MeSH Terms

Interventions

Sevelamer

Intervention Hierarchy (Ancestors)

Polyamines; Amines; Organic Chemicals

Results Point of Contact

• Title: ACTG ClinicalTrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Rajesh Gandhi, MD

  Massachusetts General Hospital ACTG CRS

  STUDY CHAIR

• Netanya Sandler, MD

  National Institutes of Health (NIH)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2012
• First Posted: March 5, 2012
• Study Start: November 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: November 1, 2012
• Last Updated: October 11, 2018
• Results First Posted: November 25, 2013

Record last verified: 2018-09

Locations

US (15)