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Sevelamer for Reducing Endotoxemia and Immune Activation

Primary Purpose

HIV-1 Infection

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sevelamer carbonate
Sevelamer carbonate
Sponsored by
AIDS Clinical Trials Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV-1 Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Alabama Therapeutics CRS (5801)
  • UCLA CARE Center CRS (601)
  • Ucsf Aids Crs (801)
  • Harbor-UCLA Med. Ctr. CRS (603)
  • University of Colorado Hospital CRS (6101)
  • Univ. of Miami AIDS CRS (901)
  • Northwestern University CRS (2701)
  • Massachusetts General Hospital ACTG CRS (101)
  • Washington University CRS (2101)
  • AIDS Care CRS (1108)
  • Univ. of Rochester ACTG CRS (1101)
  • Univ. of Cincinnati CRS (2401)
  • Case CRS (2501)
  • Metro Health CRS (2503)
  • Hosp. of the Univ. of Pennsylvania CRS (6201)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sevelamer carbonate

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change in Endotoxin
Change in endotoxin from baseline to week 4, where baseline value is the average of pre-entry and entry
Change in Endotoxin
Change in endotoxin from week 8 to week 16
Change in sCD14
Change in sCD14 from baseline to week 4, where baseline value is the average of pre-entry and entry
Change in sCD14
Change in sCD14 from week 8 to week 16
Change in CD4+ T-cell Activation
Change from baseline to week 8 in CD4+ T-cell activation, defined as the %CD38+/HLA-DR+, where baseline value is the average of pre-entry and entry
Change in CD4+ T-cell Activation
Change from baseline to week 4 in CD4+ T-cell activation, defined as the %CD38+/HLA-DR+, where baseline value is the average of pre-entry and entry
Change in CD4+ T-cell Activation
Change from week 8 to week 16 in CD4+ T-cell activation, defined as the %CD38+/HLA-DR+
Change in CD8+ T-cell Activation
Change from baseline to week 4 in CD8+ T-cell activation, defined as the %CD38+/HLA-DR+, where baseline value is the average of pre-entry and entry
Change in CD8+ T-cell Activation
Change in CD8+ T-cell activation defined as the %CD38+/HLA-DR+ from baseline to week 8, where baseline is the average of pre-entry and entry
Change in CD8+ T-cell Activation
Change in CD8+ T-cell activation defined as the %CD38+/HLA-DR+ from week 8 to week 16
Change in Proportion of Cycling CD8+
Change from baseline to week 4 in cycling CD8+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Change in Proportion of Cycling CD8+
Change from baseline to week 8 in cycling CD8+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Change in Proportion of Cycling CD8+
Change from week 8 to week 16 in cycling CD8+ , defined as the %Ki67+
Change in Proportion of Cycling CD4+
Change from baseline to week 4 in cycling CD4+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Change in Proportion of Cycling CD4+
Change from baseline to week 8 in cycling CD4+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Change in Proportion of Cycling CD4+
Change from week 8 to week 16 in cycling CD4+ , defined as the %Ki67+
Change in Blood Phosphate Levels
Change in blood phosphate levels from baseline to week 4, where baseline value is the average of pre-entry and entry
Change in Blood Phosphate Levels
Change in blood phosphate levels from baseline to week 8
Change in Blood Phosphate Levels
Change in blood phosphate levels from week 8 to week 16
Change in log10 HIV RNA Levels
Change in log10 HIV RNA levels from baseline to week 4, where baseline value is the average of pre-entry and entry
Change in log10 HIV RNA Levels
Change in log10 HIV RNA levels from baseline to week 8, where baseline value is the average of pre-entry and entry
Change in log10 HIV RNA Levels
Change in log10 HIV RNA levels from week 8 to week 16
Change in CD4+ T-cell Counts
Change in CD4+ T-cell counts from baseline to week 4, where baseline is the average of pre-entry and entry
Change in CD4+ T-cell Counts
Change in CD4+ T-cell counts from baseline to week 8, where baseline is the average of pre-entry and entry
Change in CD4+ T-cell Counts
Change in CD4+ T-cell counts from week 8 to week 16
Change in IL-6
Changes in levels of systemic inflammation marker IL-6 from baseline to week 4, where baseline is the average of pre-entry and entry
Change in IL-6
Changes in levels of systemic inflammation marker IL-6 from baseline to week 8, where baseline is the average of pre-entry and entry
Change in IL-6
Changes in levels of systemic inflammation marker IL-6 from week 8 to week 16
Change in C-reactive Protein (CRP)
Changes in levels of systemic inflammation marker CRP from baseline to week 4, where baseline is the average of pre-entry and entry
Change in CRP
Changes in levels of systemic inflammation marker CRP from baseline to week 8, where baseline is the average of pre-entry and entry
Change in CRP
Changes in levels of systemic inflammation marker CRP from week 8 to week 16, where baseline is the average of pre-entry and entry
Change in D-dimer
Change in levels of coagulation biomarker d-dimer from baseline to week 4, where baseline value is the average of pre-entry and entry
Change in D-dimer
Change in levels of coagulation biomarker d-dimer from baseline to week 8, where baseline value is the average of pre-entry and entry
Change in D-dimer
Change in levels of coagulation biomarker d-dimer from week 8 to week 16
Change in Tissue Factor
Change in levels of coagulation biomarker tissue factor from baseline to week 4, where baseline value is the average of pre-entry and entry
Change in Tissue Factor
Change in levels of coagulation biomarker tissue factor from baseline to week 8, where baseline value is the average of pre-entry and entry
Change in Tissue Factor
Change in levels of coagulation biomarker tissue factor from week 8 to week 16
Change in Total Cholesterol
Change in total cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Change in Total Cholesterol
Change in total cholesterol from week 8 to week 16
Change in LDL Cholesterol
Change in fasting LDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Change in LDL Cholesterol
Change in fasting LDL cholesterol from week 8 to week 16
Change in HDL Cholesterol
Change in fasting HDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Change in HDL Cholesterol
Change in fasting HDL cholesterol from week 8 to week 16
Change in Non-HDL Cholesterol
Change in non-HDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Change in Non-HDL Cholesterol
Change in non-HDL cholesterol from week 8 to week 16
Change in Fasting Glucose
Change in fasting glucose from baseline to week 8, where baseline value is the average of pre-entry and entry
Change in Fasting Glucose
Change in fasting glucose from week 8 to week 16
Primary Adverse Events
Number of subjects experiencing primary adverse events, defined as all reported Grade ≥ 2 signs and symptoms, Grade ≥ 2 laboratory abnormalities and other serious adverse events (SAEs)

Full Information

First Posted
February 29, 2012
Last Updated
September 11, 2018
Sponsor
AIDS Clinical Trials Group
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT01543958
Brief Title
Sevelamer for Reducing Endotoxemia and Immune Activation
Official Title
Sevelamer Carbonate for Reducing Endotoxemia and Immune Activation: A Proof of Concept Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AIDS Clinical Trials Group
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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. A5296 is a phase II, single-arm study to evaluate the effect of 8 weeks of sevelamer carbonate administration on markers of microbial translocation as well as monocyte and T-cell activation in the blood in chronically HIV-infected subjects with CD4+ T-cell count ≥ 400 cells/mm3 not receiving ART. This study enrolled 40 subjects. To assess whether there is a persistent effect of study drug, subjects were observed for an additional 8 weeks off sevelamer carbonate and changes in biomarkers were monitored. As A5296 is a phase II study of biologic activity, the primary and secondary analyses are as-treated, limited to subjects who have data for baseline and week 8 and who remain on study treatment through week 8. For any subject who initiated antiretroviral treatment (ART), analyses only included data collected prior to the time ART was started.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1 Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sevelamer carbonate
Arm Type
Experimental
Arm Description
Patients will be administered two 800 mg tablets of Sevelamer carbonate orally three times a day for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Sevelamer carbonate
Other Intervention Name(s)
Renvela
Intervention Description
Patients will be administered two 800 mg tablets of Sevelamer carbonate orally three times a day for 8 weeks.
Intervention Type
Device
Intervention Name(s)
Sevelamer carbonate
Other Intervention Name(s)
Renvela
Primary Outcome Measure Information:
Title
Change in Endotoxin
Description
Change in LPS from baseline to week 8, where baseline value is the average of pre-entry and entry values.
Time Frame
baseline and Week 8
Title
Change in Soluble CD14 (sCD14)
Description
Change in soluble CD14 (sCD14) from baseline to week 8, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Secondary Outcome Measure Information:
Title
Change in Endotoxin
Description
Change in endotoxin from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in Endotoxin
Description
Change in endotoxin from week 8 to week 16
Time Frame
week 8 and week 16
Title
Change in sCD14
Description
Change in sCD14 from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in sCD14
Description
Change in sCD14 from week 8 to week 16
Time Frame
week 8 and week 16
Title
Change in CD4+ T-cell Activation
Description
Change from baseline to week 8 in CD4+ T-cell activation, defined as the %CD38+/HLA-DR+, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in CD4+ T-cell Activation
Description
Change from baseline to week 4 in CD4+ T-cell activation, defined as the %CD38+/HLA-DR+, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in CD4+ T-cell Activation
Description
Change from week 8 to week 16 in CD4+ T-cell activation, defined as the %CD38+/HLA-DR+
Time Frame
week 8 and week 16
Title
Change in CD8+ T-cell Activation
Description
Change from baseline to week 4 in CD8+ T-cell activation, defined as the %CD38+/HLA-DR+, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in CD8+ T-cell Activation
Description
Change in CD8+ T-cell activation defined as the %CD38+/HLA-DR+ from baseline to week 8, where baseline is the average of pre-entry and entry
Time Frame
Baseline and Week 8
Title
Change in CD8+ T-cell Activation
Description
Change in CD8+ T-cell activation defined as the %CD38+/HLA-DR+ from week 8 to week 16
Time Frame
week 8 and week 16
Title
Change in Proportion of Cycling CD8+
Description
Change from baseline to week 4 in cycling CD8+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in Proportion of Cycling CD8+
Description
Change from baseline to week 8 in cycling CD8+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in Proportion of Cycling CD8+
Description
Change from week 8 to week 16 in cycling CD8+ , defined as the %Ki67+
Time Frame
from week 8 to week 16
Title
Change in Proportion of Cycling CD4+
Description
Change from baseline to week 4 in cycling CD4+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in Proportion of Cycling CD4+
Description
Change from baseline to week 8 in cycling CD4+ , defined as the %Ki67+, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in Proportion of Cycling CD4+
Description
Change from week 8 to week 16 in cycling CD4+ , defined as the %Ki67+
Time Frame
week 8 and week 16
Title
Change in Blood Phosphate Levels
Description
Change in blood phosphate levels from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame
from baseline to week 4
Title
Change in Blood Phosphate Levels
Description
Change in blood phosphate levels from baseline to week 8
Time Frame
Baseline to Week 8
Title
Change in Blood Phosphate Levels
Description
Change in blood phosphate levels from week 8 to week 16
Time Frame
from week 8 to week 16
Title
Change in log10 HIV RNA Levels
Description
Change in log10 HIV RNA levels from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in log10 HIV RNA Levels
Description
Change in log10 HIV RNA levels from baseline to week 8, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in log10 HIV RNA Levels
Description
Change in log10 HIV RNA levels from week 8 to week 16
Time Frame
week 8 and week 16
Title
Change in CD4+ T-cell Counts
Description
Change in CD4+ T-cell counts from baseline to week 4, where baseline is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in CD4+ T-cell Counts
Description
Change in CD4+ T-cell counts from baseline to week 8, where baseline is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in CD4+ T-cell Counts
Description
Change in CD4+ T-cell counts from week 8 to week 16
Time Frame
week 8 and week 16
Title
Change in IL-6
Description
Changes in levels of systemic inflammation marker IL-6 from baseline to week 4, where baseline is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in IL-6
Description
Changes in levels of systemic inflammation marker IL-6 from baseline to week 8, where baseline is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in IL-6
Description
Changes in levels of systemic inflammation marker IL-6 from week 8 to week 16
Time Frame
week 8 and week 16
Title
Change in C-reactive Protein (CRP)
Description
Changes in levels of systemic inflammation marker CRP from baseline to week 4, where baseline is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in CRP
Description
Changes in levels of systemic inflammation marker CRP from baseline to week 8, where baseline is the average of pre-entry and entry
Time Frame
Baseline and Week 8
Title
Change in CRP
Description
Changes in levels of systemic inflammation marker CRP from week 8 to week 16, where baseline is the average of pre-entry and entry
Time Frame
week 8 and week 16
Title
Change in D-dimer
Description
Change in levels of coagulation biomarker d-dimer from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in D-dimer
Description
Change in levels of coagulation biomarker d-dimer from baseline to week 8, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in D-dimer
Description
Change in levels of coagulation biomarker d-dimer from week 8 to week 16
Time Frame
week 8 and week 16
Title
Change in Tissue Factor
Description
Change in levels of coagulation biomarker tissue factor from baseline to week 4, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 4
Title
Change in Tissue Factor
Description
Change in levels of coagulation biomarker tissue factor from baseline to week 8, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in Tissue Factor
Description
Change in levels of coagulation biomarker tissue factor from week 8 to week 16
Time Frame
week 8 and week 16
Title
Change in Total Cholesterol
Description
Change in total cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in Total Cholesterol
Description
Change in total cholesterol from week 8 to week 16
Time Frame
week 8 and week 16
Title
Change in LDL Cholesterol
Description
Change in fasting LDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in LDL Cholesterol
Description
Change in fasting LDL cholesterol from week 8 to week 16
Time Frame
week 8 and week 16
Title
Change in HDL Cholesterol
Description
Change in fasting HDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in HDL Cholesterol
Description
Change in fasting HDL cholesterol from week 8 to week 16
Time Frame
from week 8 to week 16
Title
Change in Non-HDL Cholesterol
Description
Change in non-HDL cholesterol from baseline to week 8, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in Non-HDL Cholesterol
Description
Change in non-HDL cholesterol from week 8 to week 16
Time Frame
week 8 and week 16
Title
Change in Fasting Glucose
Description
Change in fasting glucose from baseline to week 8, where baseline value is the average of pre-entry and entry
Time Frame
baseline and week 8
Title
Change in Fasting Glucose
Description
Change in fasting glucose from week 8 to week 16
Time Frame
week 8 and week 16
Title
Primary Adverse Events
Description
Number of subjects experiencing primary adverse events, defined as all reported Grade ≥ 2 signs and symptoms, Grade ≥ 2 laboratory abnormalities and other serious adverse events (SAEs)
Time Frame
baseline and week 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rajesh Gandhi, MD
Organizational Affiliation
Massachusetts General Hospital ACTG CRS
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Netanya Sandler, MD
Organizational Affiliation
National Institutes of Health (NIH)
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama Therapeutics CRS (5801)
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
UCLA CARE Center CRS (601)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Ucsf Aids Crs (801)
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Harbor-UCLA Med. Ctr. CRS (603)
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
University of Colorado Hospital CRS (6101)
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Univ. of Miami AIDS CRS (901)
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Northwestern University CRS (2701)
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS (101)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Washington University CRS (2101)
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
AIDS Care CRS (1108)
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Univ. of Rochester ACTG CRS (1101)
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Univ. of Cincinnati CRS (2401)
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case CRS (2501)
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Metro Health CRS (2503)
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Hosp. of the Univ. of Pennsylvania CRS (6201)
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24864123
Citation
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.
Results Reference
derived

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Sevelamer for Reducing Endotoxemia and Immune Activation

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