NCT02750059

Brief Summary

Primary objective: To compare telmisartan therapy + antiretroviral therapy (ART) versus ART alone during acute Human Immunodeficiency Virus (HIV)a infection in reducing systemic immune activation and trafficking of activated and HIV-infected cells to the central nervous system (CNS), and limiting establishment and persistence of the CNS reservoir of HIV. At 48 weeks (during the telmisartan therapy) and 72 weeks (\~6 months after cessation of telmisartan augmentation), the investigator expect subjects in the telmisartan group will have reduced levels of blood and CSF immune activation markers, reduced brain inflammation, lower CSF HIV ribonecleic acid (RNA) and improved neuropsychological testing performance. Secondary objective: In subjects who are willing to undergo the optional inguinal lymph node biopsy, the study will determine whether subjects receiving telmisartan plus ART for 48 weeks develop less lymphoid tissue fibrosis than subjects receiving ART alone for 48 weeks. Subject population: Male and female subjects age ≥ 18 years old with acute HIV infection who are identified and enrolled in SEARCH 010/RV254 protocol will be asked to co-enroll in this study. Number of subjects: 21 Duration of follow-up: 72 weeks Study design: 21 acutely HIV-infected subjects will be randomized 2:1 to treatment with telmisartan + ART (n=14) vs. ART alone (n=7) for the first 48 weeks followed by ART alone in both arms to week 72. Blood and CSF, magnetic resonance imaging (MRI), and neuropsychological testing and exam will be collected at baseline, week 48 and week 72. Inguinal lymph node biopsy is an optional procedure that will be offered at baseline and week 48.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jan 2015

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2015

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

May 30, 2015

Completed
11 months until next milestone

First Posted

Study publicly available on registry

April 25, 2016

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2018

Completed
Last Updated

September 19, 2019

Status Verified

September 1, 2019

Enrollment Period

3.1 years

First QC Date

May 30, 2015

Last Update Submit

September 17, 2019

Conditions

Acute HIV InfectionHIV CNS Involvement

Outcome Measures

Primary Outcomes (1)

  • Difference between study arms at weeks 48 and 72 in CSF neopterin

    48 and 72 weeks

Secondary Outcomes (11)

  • Difference between study arms in lymphoid tissue fibrosis at week 48

    48 weeks

  • Difference between study arms at weeks 48 and 72 in brain inflammation by magnetic resonance spectroscopy (MRS)

    48 and 72 weeks

  • Difference between study arms at weeks 48 and 72 in CSF HIV RNA by single copy assay

    48 and 72 weeks

  • Difference between study arms at weeks 48 and 72 in aggregate neuropsychological testing performance score (NPZ-4) on Grooved Pegboard, Color Trails 1, Color Trails 2 and Trail Making A

    48 and 72 weeks

  • Difference between study arms at weeks 48 and 72 in CSF monocyte chemoattractant protein-1 (MCP-1) levels

    48 and 72 weeks

  • +6 more secondary outcomes

Study Arms (2)

TDF/3TC/EFV + Telmisartan

EXPERIMENTAL

The subjects will receive 40mg telmisartan daily for 4 weeks followed by 80mg telmisartan daily for 44 weeks in addition to ART

Drug: TDF/3TC/EFV + Telmisartan

TDF/3TC/EFV only

ACTIVE COMPARATOR

Subjects will receive ART only

Drug: TDF/3TC/EFV only

Interventions

TDF/3TC/EFV + TelmisartanDRUG

The subject will receive 40mg telmisartan daily for 4 weeks followed by 80mg telmisartan daily for 44 weeks in addition to ART. Subjects unable to tolerate 80mg of telmisartan will be able to de-escalate to 40mg daily

Also known as: tenofovir/lamivudine/efavirenz + Micardis
TDF/3TC/EFV + Telmisartan
TDF/3TC/EFV onlyDRUG

Starting from the first visit, all participants will be placed on an ART regimen to treat HIV. This is the standard route of care for HIV patients.

Also known as: tenofovir/lamivudine/efavirenz
TDF/3TC/EFV only

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18 years old
  • Have protocol-defined acute HIV-1 infection (Tested 4th generation HIV enzyme immunoassay \[EIA\] negative and NAT positive or tested 4th generation HIV EIA positive, negative by less sensitive EIA and nucleic acid testing \[NAT\] positive)
  • Be part of the SEARCH 010/RV 254 study
  • Ability and willingness to start ART immediately after diagnosis
  • Understand the study and sign informed 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
  • 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

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 (ANC) \< 750 cells/mm3, hemoglobin \<10 gm/dL creatinine clearance\<30mL/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 II receptor blocker (ARB)
  • Need for ongoing potassium supplementation
  • Any contraindication to lumbar puncture such as history of bleeding diathesis or known cerebral mass lesion

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

SEARCH Thailand

Bangkok, 10330, Thailand

Location

MeSH Terms

Interventions

TelmisartanTenofovir

Intervention Hierarchy (Ancestors)

Biphenyl CompoundsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsBenzimidazolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsOrganophosphonatesOrganophosphorus CompoundsAdeninePurines

Study Officials

  • Nittaya Phanuphak, MD, PhD

    SEARCH Research Foundation

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Nittaya Phanuphak, MD, PhD

Study Record Dates

First Submitted

May 30, 2015

First Posted

April 25, 2016

Study Start

January 1, 2015

Primary Completion

February 1, 2018

Study Completion

February 1, 2018

Last Updated

September 19, 2019

Record last verified: 2019-09

Locations

TH(1)