Acute HIV InfectionPhase 1SEARCH018NCT02170246
Analysis of Telmisartan Administered With Antiretroviral Therapy (ART) in Patients With Acute HIV Infection
A Phase 1 study testing Telmisartan in people with Acute HIV Infection and HIV Infections, run by Yale University at 2 sites in Thailand.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute HIV Infection, HIV Infections
- What is being tested?
- Telmisartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesThailand
- Study dates
- 28 Jan 2015to 13 Jun 2018
- Phase
- Phase 1
- 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
- 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.
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 < 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
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- 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
Trial locations and contacts
2 sites in 1 country.
Thailand2 sites
Chulalongkorn University Hospital
Bangkok, 10330
Thai Red Cross AIDS Research Centre
Bangkok, 10330
About this study
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]
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.
Read the 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.
- Conditions
- Acute HIV Infection, HIV Infections
- Being tested
- Telmisartan
- Keywords
- Acute HIV infection, Central nervous system, Antiretroviral therapy, Telmisartan, Cerebrospinal fluid
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TelmisartanDrug
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Telmisartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: 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)
Will assess blood plasma levels of these biomarkers in subjects on ART + telmisartan versus those on ART only.
Measured: 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
These measurements will be made using magnetic resonance spectroscopy (MRS).
Measured: Change from baseline to 48 weeks following ART initiation
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.
Measured: Change from baseline to 48 weeks following ART initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2014 (estimated)
- Study start28 Jan 2015
- Primary completion13 Jun 2018
- Study completion13 Jun 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.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- 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)
- Responsible party
- Sponsor
- Investigators
- Serena Spudich, MD, MA, Principal investigator, Yale UniversityJintanat Ananworanich, MD, PhD, Study chair, U.S. Military HIV Research Program, Bethesda, MarylandNittaya Phanuphak, MD, PhD, Principal investigator, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02170246
- Sponsor's protocol ID
- 1401013214
- Other IDs
- 1R01NS084911-01, W81XWH-11-2-0174, R01MH095613, R01MH104141
- Acronym
- SEARCH018
- Status last verified
- Mar 2020
- First submitted
- 22 May 2014
- Last updated
- 9 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2020. 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 Central Nervous System Reservoirs of HIV and Lymph Node Fibrosis [Southeast Asia Research Collaboration With Hawaii (SEARCH) 018]
- ClinicalTrials.gov ID
- NCT02170246
- Acronym / sponsor ID
- SEARCH018 / 1401013214
- Conditions
- Acute HIV Infection, HIV Infections
- Keywords
- Acute HIV infection, Central nervous system, Antiretroviral therapy, Telmisartan, Cerebrospinal fluid
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- 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)
- Study start
- 28 Jan 2015 (actual)
- Primary completion
- 13 Jun 2018 (actual)
- Study completion
- 13 Jun 2018 (actual)
- First posted
- 23 Jun 2014 (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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: TelmisartanAcute 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
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 < 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
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 |
|---|---|---|
| Telmisartan | Drug | ART + Telmisartan |
Primary outcome
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.
4 secondary outcomes
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
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
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
Test scores on HIV neuropsychological battery
Time frame: Change from baseline to 48 weeks following ART initiation
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 9 Mar 2020.
- Website: South East Asia Research Collaboration with HawaiiLink provided by the sponsor.
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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.
Serena Spudich, MD, MA principal investigator
Yale University
Jintanat Ananworanich, MD, PhD study chair
U.S. Military HIV Research Program, Bethesda, Maryland
Nittaya Phanuphak, MD, PhD principal investigator
Thai Red Cross AIDS Research Centre, Bangkok, Thailand
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Telmisartan in people with Acute HIV Infection and HIV Infections, run by Yale University at 2 sites 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 8 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 9 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
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). 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 9 Mar 2020.