search
Back to results

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

Primary Purpose

Acute HIV Infection, HIV Infections

Status
Completed
Phase
Phase 1
Locations
Thailand
Study Type
Interventional
Intervention
Telmisartan
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Acute HIV Infection focused on measuring Acute HIV infection, Central nervous system, Antiretroviral therapy, Telmisartan, Cerebrospinal fluid

Eligibility Criteria

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

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

Sites / Locations

  • Chulalongkorn University Hospital
  • Thai Red Cross AIDS Research Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Antiretroviral Therapy (ART) only

ART + Telmisartan

Arm Description

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.

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).

Outcomes

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
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)
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)
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
These measurements will be made using magnetic resonance spectroscopy (MRS).
Test scores on HIV neuropsychological battery
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.

Full Information

First Posted
May 22, 2014
Last Updated
March 4, 2020
Sponsor
Yale University
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), SEARCH Research Foundation, University of California, San Francisco, Walter Reed Army Institute of Research (WRAIR), University of Hawaii, National Institute of Mental Health (NIMH)
search

1. Study Identification

Unique Protocol Identification Number
NCT02170246
Brief Title
Analysis of Telmisartan Administered With Antiretroviral Therapy (ART) in Patients With Acute HIV Infection
Acronym
SEARCH018
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]
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
January 28, 2015 (Actual)
Primary Completion Date
June 13, 2018 (Actual)
Study Completion Date
June 13, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), SEARCH Research Foundation, University of California, San Francisco, Walter Reed Army Institute of Research (WRAIR), University of Hawaii, National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute HIV Infection, HIV Infections
Keywords
Acute HIV infection, Central nervous system, Antiretroviral therapy, Telmisartan, Cerebrospinal fluid

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Antiretroviral Therapy (ART) only
Arm Type
No Intervention
Arm Description
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.
Arm Title
ART + Telmisartan
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Telmisartan
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Change from baseline to 48 weeks following ART initiation
Secondary Outcome Measure Information:
Title
Change in levels of mast cell progenitor-1 (MCP-1), IP-10, and HIV RNA in the cerebrospinal fluid (CSF)
Description
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.
Time Frame
Change from baseline to 48 weeks following ART initiation
Title
Change in blood plasma levels of neopterin, interleukin-6, D-dimers, soluble cluster of differentiation 14 (sCD14), and soluble cluster of differentiation 163 (sCD163)
Description
Will assess blood plasma levels of these biomarkers in subjects on ART + telmisartan versus those on ART only.
Time Frame
Change from baseline to 48 weeks following ART initiation
Title
Change in absolute concentrations and ratios with respect to creatine of choline, myoinositol, and n-acetylaspartate (NAA) in specified brain regions
Description
These measurements will be made using magnetic resonance spectroscopy (MRS).
Time Frame
Change from baseline to 48 weeks following ART initiation
Title
Test scores on HIV neuropsychological battery
Description
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.
Time Frame
Change from baseline to 48 weeks following ART initiation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Serena Spudich, MD, MA
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jintanat Ananworanich, MD, PhD
Organizational Affiliation
U.S. Military HIV Research Program, Bethesda, Maryland
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Nittaya Phanuphak, MD, PhD
Organizational Affiliation
Thai Red Cross AIDS Research Centre, Bangkok, Thailand
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chulalongkorn University Hospital
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Thai Red Cross AIDS Research Centre
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand

12. IPD Sharing Statement

Links:
URL
http://www.searchthailand.org/
Description
Website: South East Asia Research Collaboration with Hawaii

Learn more about this trial

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

We'll reach out to this number within 24 hrs