Analysis of Telmisartan Administered With Antiretroviral Therapy (ART) in Patients With Acute HIV Infection

NCT02170246 | Completed Phase 1 DMC

• 5 other identifiers: 14010132141R01NS084911-01W81XWH-11-2-0174R01MH095613R01MH104141
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

This research project will study whether the drug telmisartan administered in conjunction with antiretroviral therapy (ART) will help reduce nervous system infection with HIV. The investigators are studying the effect of this treatment in people who have contracted HIV infection within the past three weeks, and thus have a form of HIV called acute HIV infection. The investigators will measure biological markers of immune activation in the blood and cerebrospinal fluid to see if telmisartan may reduce the spread of HIV reservoirs in affected patients.

Conditions

Acute HIV Infection; HIV Infections

Keywords

Acute HIV infection; Central nervous system; Antiretroviral therapy; Telmisartan; Cerebrospinal fluid

Outcome Measures

Primary Outcomes (1)

• Change in level of neopterin in the cerebrospinal fluid (CSF) of patients placed on antiretroviral therapy (ART) administered in conjunction with telmisartan, versus those placed on ART only

  Neopterin is a biological marker of immune activation. Its presence in the CSF provides information on the establishment and persistence of HIV viral reservoirs within the central nervous system of HIV-positive patients.

  Change from baseline to 48 weeks following ART initiation

Secondary Outcomes (4)

• Change in levels of mast cell progenitor-1 (MCP-1), IP-10, and HIV RNA in the cerebrospinal fluid (CSF)

  Change from baseline to 48 weeks following ART initiation

• Change in blood plasma levels of neopterin, interleukin-6, D-dimers, soluble cluster of differentiation 14 (sCD14), and soluble cluster of differentiation 163 (sCD163)

  Change from baseline to 48 weeks following ART initiation

• Change in absolute concentrations and ratios with respect to creatine of choline, myoinositol, and n-acetylaspartate (NAA) in specified brain regions

  Change from baseline to 48 weeks following ART initiation

• Test scores on HIV neuropsychological battery

  Change from baseline to 48 weeks following ART initiation

Study Arms (2)

Antiretroviral Therapy (ART) only

NO INTERVENTION

Acute HIV-infected subjects (n=7) will be randomly assigned to a group that will receive antiretroviral therapy (the current standard of care for HIV patients) for 72 weeks.

ART + Telmisartan

EXPERIMENTAL

Acute HIV-infected subjects (n=14) will be randomly assigned to a group that will receive treatment with telmisartan in addition to ART. Subjects will receive 40mg telmisartan daily for 4 weeks, followed by 80mg telmisartan daily for 44 weeks, to be taken in conjunction with ART. Subjects unable to tolerate 80mg of telmisartan will be able to de-escalate to 40mg daily. After telmisartan is stopped, subjects will continue to take ART for an additional 24 weeks (total 72 weeks).

Drug: Telmisartan

Interventions

Telmisartan DRUG

ART + Telmisartan

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old
• Have protocol-defined acute HIV-1 infection
• Be part of the SEARCH 010/RV 254 study in Bangkok, Thailand
• Ability and willingness to start ART immediately after diagnosis
• Availability for follow-up for the duration of the planned study
• Systolic blood pressure ≥ 110 mmHg
• Agree to undergo lumbar puncture at weeks 0, 48 and 72
• Ability and willingness to provide informed consent. Subjects must understand the study and sign the consent form. Persons who cannot read will have the consent form read to them by a member of the study staff and may then give informed consent by using making a thumb print.

You may not qualify if:

• Pregnancy (current or within the last 6 months) or breastfeeding
• Uncontrolled hypertension
• Use of thiazolidinediones or other angiotensin receptor blockers class \[losartan, irbesartan, olmesartan, valsartan, candesartan (washout permitted)\]
• Screening laboratory values: absolute neutrophil count \< 750 cells/mm3, hemoglobin \<10 gm/dL creatinine clearance \<30 mL/min (estimated by the Cockcroft-Gault equation using ideal body weight)
• Known renal artery stenosis
• Known cirrhosis or severe liver disease
• Unstable coronary artery disease/angina or decompensated congestive heart failure
• Any history of intolerance to any angiotensin receptor blocker
• Need for ongoing potassium supplementation
• Any contraindication to lumbar puncture such as history of bleeding diathesis or cerebral mass lesion

Sponsors & Collaborators

• Yale University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• SEARCH Research Foundation: collaborator
• University of California, San Francisco: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator
• University of Hawaii: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Chulalongkorn University Hospital

Bangkok, 10330, Thailand

Location

Thai Red Cross AIDS Research Centre

Bangkok, 10330, Thailand

Location

Related Links

• Website: South East Asia Research Collaboration with Hawaii

MeSH Terms

Conditions

HIV Infections

Interventions

Telmisartan

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Serena Spudich, MD, MA

  Yale University

  PRINCIPAL INVESTIGATOR

• Jintanat Ananworanich, MD, PhD

  U.S. Military HIV Research Program, Bethesda, Maryland

  STUDY CHAIR

• Nittaya Phanuphak, MD, PhD

  Thai Red Cross AIDS Research Centre, Bangkok, Thailand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2014
• First Posted: June 23, 2014
• Study Start: January 28, 2015
• Primary Completion: June 13, 2018
• Study Completion: June 13, 2018
• Last Updated: March 9, 2020

Record last verified: 2020-03

Locations

TH (2)