Acute HIV InfectionPhase 2NCT02750059
Using Telmisartan With ART During Acute HIV Infection to Reduce the CNS Reservoirs of HIV and Lymph Node Fibrosis
A Phase 2 study testing TDF/3TC/EFV + Telmisartan and TDF/3TC/EFV only in people with Acute HIV Infection and HIV CNS Involvement, run by SEARCH Research Foundation at 1 site in Thailand.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute HIV Infection, HIV CNS Involvement
- What is being tested?
- TDF/3TC/EFV + Telmisartan and TDF/3TC/EFV only
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteThailand
- Study dates
- Jan 2015to Feb 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Systolic blood pressure ≥ 110 mmHg
- Agree to undergo lumbar puncture at weeks 0, 48 and 72
- Ability and willingness to provide informed consent
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Adjunctive Therapy With Telmisartan Instituted With ART During Acute HIV Infection to Reduce the Establishment of CNS Reservoirs of HIV and Lymph Node Fibrosis
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.
Read more
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.
Read the detailed description
Clinical assessments:
Neurological exam: South East Asia Research Collaboration with Hawaii (SEARCH) employs the AIDS Clinical Trials Group (ACTG)-derived HIV macroneurological examination, a physician rated symptoms assessment of cognitive features typical of HAND and peripheral neuropathy
Neuropsychological assessments: SEARCH employs the HIV neurocognitive battery originally developed by Maj et al. designed to minimize cultural bias and tested in Bangkok. All subjects will have the full SEARCH battery as previously published, avoiding evaluations following invasive procedures.
Quantification of Drug use: Drug and alcohol use are assessed with a structured interview including methamphetamine, heroin, and marijuana based on a Thai Red Cross study defining frequently abused drugs in Bangkok. Urine is stored at each visit and may be later tested for illicit drugs. Evidence of intoxication is documented so that neuropsychological data can be censored.
Lumbar punctures are completed per standard clinical procedures using a Sprotte® (pencil-point) needle to minimize complications. Standard assessments of CSF and serum, protein and cell count are completed and approximately 20cc are collected and ultra-centrifuged, Cell pellets of both blood and CSF will be cryopreserved for future potential studies, with subject consent. Supernatants are divided into 0.5cc aliquots, and frozen to -80oC on the same day. Venereal Disease Research Laboratory test (VDRL)/Rapid Plasma Reagin (RPR) will be assessed at baseline and in follow up if risk for new syphilis exposure is reported. Participant hospitalization for hydration will be completed, if needed. Participants will be compensated for their time based on Institutional Review Board (IRB)-approved rates.
- Conditions
- Acute HIV Infection, HIV CNS Involvement
- Being tested
- TDF/3TC/EFV + Telmisartan, TDF/3TC/EFV only
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TDF/3TC/EFV + TelmisartanDrug
Also called tenofovir/lamivudine/efavirenz + Micardis
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
TDF/3TC/EFV onlyDrug
Also called tenofovir/lamivudine/efavirenz
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: TDF/3TC/EFV + Telmisartan |
| TDF/3TC/EFV only | Active comparator | Subjects will receive ART only Receives: Drug: TDF/3TC/EFV only |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference between study arms at weeks 48 and 72 in CSF neopterin
Measured: 48 and 72 weeks
Secondary outcomes (11)
Difference between study arms in lymphoid tissue fibrosis at week 48
Measured: 48 weeks
Difference between study arms at weeks 48 and 72 in brain inflammation by magnetic resonance spectroscopy (MRS)
Measured: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in CSF HIV RNA by single copy assay
Measured: 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
Measured: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in CSF monocyte chemoattractant protein-1 (MCP-1) levels
Measured: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in CSF interferon-gamma-inducible protein-10 (IP-10) levels
Measured: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in plasma neopterin levels
Measured: 72 weeks
Difference between study arms at weeks 48 and 72 in plasma soluable CD14 (sCD14) levels
Measured: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in plasma interleukin-6 (IL-6) levels
Measured: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in plasma D-dimer levels
Measured: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in plasma soluable CD163 (sCD163) levels
Measured: 48 and 72 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2016 (estimated)
- Study startJan 2015
- Primary completionFeb 2018
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- SEARCH Research Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nittaya Phanuphak, MD, PhD, SEARCH Research Foundation
- Investigators
- Nittaya Phanuphak, MD, PhD, Principal investigator, SEARCH Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02750059
- Sponsor's protocol ID
- SEARCH 018
- Other IDs
- 1R01NS084911-01
- Status last verified
- Sep 2019
- First submitted
- 30 May 2015
- Last updated
- 19 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Therapy With Telmisartan Instituted With ART During Acute HIV Infection to Reduce the Establishment of CNS Reservoirs of HIV and Lymph Node Fibrosis
- ClinicalTrials.gov ID
- NCT02750059
- Acronym / sponsor ID
- SEARCH 018
- Conditions
- Acute HIV Infection, HIV CNS Involvement
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- SEARCH Research FoundationUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jan 2015
- Primary completion
- Feb 2018 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 25 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Clinical assessments:
Neurological exam: South East Asia Research Collaboration with Hawaii (SEARCH) employs the AIDS Clinical Trials Group (ACTG)-derived HIV macroneurological examination, a physician rated symptoms assessment of cognitive features typical of HAND and peripheral neuropathy
Neuropsychological assessments: SEARCH employs the HIV neurocognitive battery originally developed by Maj et al. designed to minimize cultural bias and tested in Bangkok. All subjects will have the full SEARCH battery as previously published, avoiding evaluations following invasive procedures.
Quantification of Drug use: Drug and alcohol use are assessed with a structured interview including methamphetamine, heroin, and marijuana based on a Thai Red Cross study defining frequently abused drugs in Bangkok. Urine is stored at each visit and may be later tested for illicit drugs. Evidence of intoxication is documented so that neuropsychological data can be censored.
Lumbar punctures are completed per standard clinical procedures using a Sprotte® (pencil-point) needle to minimize complications. Standard assessments of CSF and serum, protein and cell count are completed and approximately 20cc are collected and ultra-centrifuged, Cell pellets of both blood and CSF will be cryopreserved for future potential studies, with subject consent. Supernatants are divided into 0.5cc aliquots, and frozen to -80oC on the same day. Venereal Disease Research Laboratory test (VDRL)/Rapid Plasma Reagin (RPR) will be assessed at baseline and in follow up if risk for new syphilis exposure is reported. Participant hospitalization for hydration will be completed, if needed. Participants will be compensated for their time based on Institutional Review Board (IRB)-approved rates.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TDF/3TC/EFV + Telmisartan | Experimental | Drug: TDF/3TC/EFV + TelmisartanThe subjects will receive 40mg telmisartan daily for 4 weeks followed by 80mg telmisartan daily for 44 weeks in addition to ART |
| TDF/3TC/EFV only | Active comparator | Drug: TDF/3TC/EFV onlySubjects will receive ART only |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TDF/3TC/EFV + TelmisartanAlso: tenofovir/lamivudine/efavirenz + MicardisThe 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 | Drug | TDF/3TC/EFV + Telmisartan |
| TDF/3TC/EFV onlyAlso: tenofovir/lamivudine/efavirenzStarting 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. | Drug | TDF/3TC/EFV only |
Primary outcome
Difference between study arms at weeks 48 and 72 in CSF neopterin
Time frame: 48 and 72 weeks
11 secondary outcomes
Difference between study arms in lymphoid tissue fibrosis at week 48
Time frame: 48 weeks
Difference between study arms at weeks 48 and 72 in brain inflammation by magnetic resonance spectroscopy (MRS)
Time frame: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in CSF HIV RNA by single copy assay
Time frame: 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
Time frame: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in CSF monocyte chemoattractant protein-1 (MCP-1) levels
Time frame: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in CSF interferon-gamma-inducible protein-10 (IP-10) levels
Time frame: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in plasma neopterin levels
Time frame: 72 weeks
Difference between study arms at weeks 48 and 72 in plasma soluable CD14 (sCD14) levels
Time frame: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in plasma interleukin-6 (IL-6) levels
Time frame: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in plasma D-dimer levels
Time frame: 48 and 72 weeks
Difference between study arms at weeks 48 and 72 in plasma soluable CD163 (sCD163) levels
Time frame: 48 and 72 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nittaya Phanuphak, MD, PhD principal investigator
SEARCH Research Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TDF/3TC/EFV + Telmisartan and TDF/3TC/EFV only in people with Acute HIV Infection and HIV CNS Involvement, run by SEARCH Research Foundation at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference between study arms at weeks 48 and 72 in CSF neopterin (time frame: 48 and 72 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2019.