NCT01852942

Reversing Tissue Fibrosis to Improve Immune Reconstitution in HIV

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (actual)
• Sponsor: University of Minnesota · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

This study was designed to test the hypothesis that treatment of HIV infected subjects with losartan, an agent with specific anti-inflammatory and anti-fibrotic actions, will: 1. reverse existing lymphoid tissue fibrosis, 2. restore lymphoid tissue architecture, 3. increase the number and improve the function of peripheral and lymphatic CD4 T cells, 4. decrease levels of systemic immune activation (IA), 5. decrease size of the HIV reservoir, and 6. be safe and well tolerated.

Detailed description

This is a randomized, double-blind, placebo-controlled trial of 50 HIV-1 infected individuals on stable ART randomized in a 1:1 ratio to losartan (50 mg orally daily titrated to 100 mg daily) vs placebo for 30 months. We plan to enroll a total of 63 HIV infected subjects to ensure that 50 complete the protocol. All HIV infected subjects will undergo biopsies of inguinal lymph node (LN) and gut associated lymphatic tissue (GALT) for primary endpoint analysis at baseline, 12 and 30 months after study enrollment. Blood will be collected at least quarterly throughout the study and an intensive blood pharmacokinetic (PK) study will be conducted at month 1. All HIV infected subjects will be vaccinated with the quadrivalent human papillomavirus (HPV) vaccine at months 23, 25 and 29.5 to measure immune function. 5 HIV uninfected control subjects will also be enrolled. The primary endpoint is to determine the impact of losartan on lymphoid tissue fibrosis in HIV infected, ART treated adults. This will be determined by measuring the amount of collagen deposition in lymphoid tissues and the integrity of the FRCn using immunohistochemistry (IHC) and quantitative image analysis (QIA).

Conditions

• HIV Infection
• HIV Infections

Interventions

Type	Name	Description
DRUG	Losartan	Participants will start with 50 mg of losartan by mouth daily. The dose will be increased to 100 mg by mouth daily after 14 days. The maximal tolerable dosage (up to 100mg by mouth daily) will be continued for a total of 30 months.
DRUG	Placebo	one tablet by mouth daily

Timeline

• Start date: 2014-09-01
• Primary completion: 2019-07-16
• Completion: 2019-07-16
• First posted: 2013-05-14
• Last updated: 2020-12-11
• Results posted: 2020-12-11

Locations

1 site across 1 country: United States