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Analysis of Telmisartan Administered With Antiretroviral Therapy (ART) in Patients With Acute HIV Infection (SEARCH018)

This study is currently recruiting participants.
Verified January 2015 by Serena Spudich, MD, Yale University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02170246
First Posted: June 23, 2014
Last Update Posted: January 26, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
South East Asia Research Collaboration with Hawaii
University of California, San Francisco
Walter Reed Army Institute of Research (WRAIR)
University of Hawaii
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Serena Spudich, MD, Yale University
  Purpose
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.

Condition Intervention Phase
Acute HIV Infection HIV Infections Drug: Telmisartan Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Official Title: Adjunctive Therapy With Telmisartan Instituted With ART During Acute HIV Infection to Reduce the Establishment of Central Nervous System Reservoirs of HIV and Lymph Node Fibrosis [Southeast Asia Research Collaboration With Hawaii (SEARCH) 018]

Resource links provided by NLM:


Further study details as provided by Serena Spudich, MD, Yale University:

Primary Outcome Measures:
  • 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 [ Time Frame: Change from baseline to 48 weeks following ART initiation ]
    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.


Secondary Outcome Measures:
  • Change in levels of mast cell progenitor-1 (MCP-1), IP-10, and HIV RNA in the cerebrospinal fluid (CSF) [ Time Frame: Change from baseline to 48 weeks following ART initiation ]
    Will assess CSF levels of MCP-1, IP-10, and HIV RNA. Absolute levels of these compounds will be compared between subjects on ART + telmisartan versus those on ART only.

  • Change in blood plasma levels of neopterin, interleukin-6, D-dimers, soluble cluster of differentiation 14 (sCD14), and soluble cluster of differentiation 163 (sCD163) [ Time Frame: Change from baseline to 48 weeks following ART initiation ]
    Will assess blood plasma levels of these biomarkers in subjects on ART + telmisartan versus those on ART only.

  • Change in absolute concentrations and ratios with respect to creatine of choline, myoinositol, and n-acetylaspartate (NAA) in specified brain regions [ Time Frame: Change from baseline to 48 weeks following ART initiation ]
    These measurements will be made using magnetic resonance spectroscopy (MRS).

  • Test scores on HIV neuropsychological battery [ Time Frame: Change from baseline to 48 weeks following ART initiation ]
    The assessments to be used in this study have been tested for use with native Thai speakers and will be consistent with other SEARCH study tests. SEARCH employs a HIV neurocognitive battery designed to minimize cultural bias, which has been tested in Bangkok.


Estimated Enrollment: 21
Study Start Date: August 2014
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Antiretroviral Therapy (ART) only
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.
Experimental: ART + Telmisartan
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

Detailed Description:
Note regarding the primary purpose of the study: In the Study Design section, this protocol is classified as "Other", since it is specifically designed to examine the effect of telmisartan administered in conjunction with ART on the size of HIV reservoirs in the central nervous system.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02170246


Locations
Thailand
Chulalongkorn University Hospital Recruiting
Bangkok, Thailand, 10330
Contact: Nittaya Phanuphak, MD, PhD    66 2 254 2566    Nittaya.p@trcarc.org   
Principal Investigator: Nittaya Phanuphak, MD, PhD         
Thai Red Cross AIDS Research Centre Recruiting
Bangkok, Thailand, 10330
Contact: Nittaya Phanuphak, MD, PhD    66 2 254 2566    Nittaya.P@trcarc.org   
Principal Investigator: Nittaya Phanuphak, MD, PhD         
Sponsors and Collaborators
Yale University
National Institute of Neurological Disorders and Stroke (NINDS)
South East Asia Research Collaboration with Hawaii
University of California, San Francisco
Walter Reed Army Institute of Research (WRAIR)
University of Hawaii
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Serena Spudich, MD, MA Yale University
Study Chair: Jintanat Ananworanich, MD, PhD U.S. Military HIV Research Program, Bethesda, Maryland
Principal Investigator: Nittaya Phanuphak, MD, PhD Thai Red Cross AIDS Research Centre, Bangkok, Thailand
  More Information

Additional Information:
Responsible Party: Serena Spudich, MD, Associate Professor of Neurology, Yale School of Medicine, Yale University
ClinicalTrials.gov Identifier: NCT02170246     History of Changes
Other Study ID Numbers: 1R01NS084911-01 ( U.S. NIH Grant/Contract )
W81XWH-11-2-0174 ( Other Identifier: Henry M. Jackson Foundation Cooperative Agreement )
R01MH095613 ( U.S. NIH Grant/Contract )
First Submitted: May 22, 2014
First Posted: June 23, 2014
Last Update Posted: January 26, 2015
Last Verified: January 2015

Keywords provided by Serena Spudich, MD, Yale University:
Acute HIV infection
Central nervous system
Antiretroviral therapy
Telmisartan
Cerebrospinal fluid

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Telmisartan
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action


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