HIV-1-infectionPhase 1/2STARNCT06282783
Studying Topiramate for Re-Activating the HIV-1 Reservoir
A Phase 1/2 study testing Topiramate in people with HIV-1-infection and Hiv, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
Even with current HIV treatments, HIV is still a lifelong disease because it hides in some long-lasting cells in the body. One of the strategies to find a cure for HIV works by finding the virus in these cells, making it visible, and then getting rid of it. This is called the 'shock and kill' approach. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1-infection, Hiv, HIV Infections
- What is being tested?
- Topiramate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2024to Aug 2025
- Phase
- Phase 1/2
- 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
- Documented HIV-1, subtype B or C
- Aged 18 or over
- On ART for a minimum of 2 consecutive years and a maximum of 12 consecutive years
- HIV-1 RNA plasma level <30 copies/mL for at least two consecutive measurements prior to inclusion (viral blips with a detectable HIVRNA 30-200 c/mL preceded and followed by HIV-RNA <30 are allowed)
- CD4+ T cell count ≥200 cells/mm^3 at screening
- Able to understand the information and give informed consent
Who cannot join
- Any major acute medical condition requiring hospitalisation within the past 4 weeks.
- Presence of an active opportunistic infection that defines Acquired Immunodeficiency Syndrome (AIDS).
- Any medical condition deemed by the investigator to hinder compliance with the study treatment.
- The following laboratory values at the screening phase (available before baseline (T0)): hepatic transaminases (AST or ALT) ≥3 times the upper limit of normal (ULN), serum total bilirubin ≥3 times the ULN, estimated glomerular filtration rate (eGFR) ≤60 mL/min based on CKD-EPI, haemoglobin <6.5 mmol/L (males) or <6.0 mmol/L (females), leucocytes <2.5 x10^9/L, absolute neutrophil count <1000 cells/mm^3, thrombocytes <100 x10^9/L
- Active malignancy during the past year except for basal carcinoma of the skin, stage 0 cervical carcinoma, Kaposi Sarcoma treated with ART alone, or other indolent malignancies.
- Participants who are unwilling or unable to use barrier contraception during sexual intercourse during the study.
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- History of suicide or suicidal ideation.
- History of ophthalmological medical problems leading to glaucoma or visual field disturbances (e.g. macula oedema). Refraction abnormalities that can be corrected by lenses are acceptable.
- History of any medical condition with a causal relationship with hyperammonemia.
- Participants using phenytoin, carbamazepine, digoxin, lithium, or valproic acid throughout the trial period.
- Any concurrent medicine use associated with hyperammonemia (e.g. valproic acid).
- Participants with active substance abuse.
- Participants who have registered allergies to the investigational medical product.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Clinical Trial Investigating the Effect of Topiramate on the Reactivation of the HIV-1 Reservoir in People Living With HIV on Antiretroviral Therapy
Even with current HIV treatments, HIV is still a lifelong disease because it hides in some long-lasting cells in the body. One of the strategies to find a cure for HIV works by finding the virus in these cells, making it visible, and then getting rid of it. This is called the 'shock and kill' approach.
So far, the drugs tested can find the virus, but they don't get rid of it completely. That's why there need to be new drugs that can do this more effectively. The Erasmus MC HIV Eradication Group (EHEG) has been testing new drugs in the lab and found a drug called topiramate can wake up the virus without harming the cells. The aim of this study is to test topiramate in people living with HIV.
Most of the people that participate in HIV cure studies are men, even though most people living with HIV around the world are women. Previous research has shown that men and women might respond differently to these treatments. So, in this study, topiramate will be investigated in both men and women. This could help us find a cure that works for everyone.
Read the detailed description
Despite antiretroviral therapy (ART), an infection with the human immunodeficiency virus 1 (HIV-1) is still a lifelong disease because of the latent HIV reservoir. This reservoir consists of a pool of long-lived cells harbouring an integrated copy of the HIV provirus in its genome. One approach to curing HIV centres on reversing viral latency, combined with the subsequent elimination of the virus from this reservoir specifically, all while safeguarding other cells through the use of ART. This approach is colloquially known as 'shock and kill'. The limited number of latency reversing agents (LRAs) that have been studied were effective at reactivating the latent reservoir, but do not result in significant reservoir reduction (Debrabander, 2023). Investigating novel LRAs is, therefore, necessary to identify more potent ways of HIV reactivation, with the ultimate goal of reservoir depletion i.e. a functional HIV cure. The Erasmus MC HIV Eradication group has set up a translational trial platform, where successfully study the effects of novel LRAs from bench to bedside. One example is the discovery of small molecule inhibitors of BAF, which reverse HIV-1 latency, to a clinical trial investigating pyrimethamine in people living with HIV (PLWH) (Stoszko, 2016; Prins, 2023). A new promising drug target that was identified in EHEG is the glutamate receptor, ionotropic kainate 5 (GRIK5); a host factor involved in HIV latency (Roling, 2021). The registered drug topiramate was identified as a potential GRIK5 inhibitor. Further ex vivo testing confirmed HIV latency reversal of topiramate at therapeutic levels without inducing cytotoxic effects. This opens new opportunities for HIV cure research. A further knowledge gap to be explored is the influence of sex in HIV latency reversal. Typically, either by design or recruitment, male participants have been vastly overrepresented in HIV cure research (Barr, 2020). This is despite previous research showing significant difference in HIV latency reversal in women (Rao, 2022), and the importance of sex in pharmacodynamics being increasingly recognised (Gandhi, 2004; Mauvais-Jarvis, 2021). As the majority of PLWH worldwide are women and their numbers are expected to grow, studies on any potential cure strategy that provide an evidence base for their use in women increase clinical impact (UNAIDS, 2023). Therefore, the aim of this study is to examine the effect and safety of topiramate as an LRA in both men and women.
- Conditions
- HIV-1-infection, Hiv, HIV Infections, HIV I Infection
- Being tested
- Topiramate
- Keywords
- HIV Cure, Shock and Kill, Topiramate, Latency Reversing Agents, Latency Reversal
- Medical subject headings
- Acquired Immunodeficiency Syndrome, HIV Infections, Shock
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopiramateDrug
Single dose of 400mg
| Study group | Role | What they receive |
|---|---|---|
| Men | Experimental | Sex assigned at birth, male Single dose of 400mg topiramate Receives: Drug: Topiramate |
| Women | Experimental | Sex assigned at birth, female Single dose of 400mg topiramate Receives: Drug: Topiramate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of topiramate as measured by cell-associated HIV RNA
To assess the effect of topiramate on HIV reactivation in people living with HIV on ART
Measured: 24 hours
Number of treatment-related adverse events as assessed by CTCAE v4.0
To evaluate the clinical safety and tolerability of topiramate
Measured: 7 days
Secondary outcomes (2)
Influence of sex on the primary outcome measures
To evaluate the influence of sex on reactivation potential as measured by cell-associated HIV RNA, and safety and tolerability of topiramate as assessed by CTCAE v4.0
Measured: 24 hours
The effect of topiramate on the size of the HIV reservoir measured by relevant assays
To assess the effect of topiramate on the size of the HIV reservoir
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2024
- Study startSep 2024 (estimated)
- Primary completionApr 2025 (estimated)
- Study completionAug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Casper Rokx, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06282783
- Sponsor's protocol ID
- 2024-511532-27-00
- Acronym
- STAR
- Status last verified
- Feb 2024
- First submitted
- 12 Feb 2024
- Last updated
- 28 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data will be stored in accordance with the FAIR use principle for potential future studies. If external researchers express interest in this dataset, they are encouraged to reach out to the lead investigator. Provided that sufficient privacy measures are in place, the data may be disseminated under a newly established Data Sharing Agreement.
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Clinical Trial Investigating the Effect of Topiramate on the Reactivation of the HIV-1 Reservoir in People Living With HIV on Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT06282783
- Acronym / sponsor ID
- STAR / 2024-511532-27-00
- Conditions
- HIV-1-infection, Hiv, HIV Infections, HIV I Infection
- Keywords
- HIV Cure, Shock and Kill, Topiramate, Latency Reversing Agents, Latency Reversal
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- Sep 2024 (estimated)
- Primary completion
- Apr 2025 (estimated)
- Study completion
- Aug 2025 (estimated)
- First posted
- 28 Feb 2024 (actual)
- 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.
Even with current HIV treatments, HIV is still a lifelong disease because it hides in some long-lasting cells in the body. One of the strategies to find a cure for HIV works by finding the virus in these cells, making it visible, and then getting rid of it. This is called the 'shock and kill' approach.
So far, the drugs tested can find the virus, but they don't get rid of it completely. That's why there need to be new drugs that can do this more effectively. The Erasmus MC HIV Eradication Group (EHEG) has been testing new drugs in the lab and found a drug called topiramate can wake up the virus without harming the cells. The aim of this study is to test topiramate in people living with HIV.
Most of the people that participate in HIV cure studies are men, even though most people living with HIV around the world are women. Previous research has shown that men and women might respond differently to these treatments. So, in this study, topiramate will be investigated in both men and women. This could help us find a cure that works for everyone.
Detailed description
Despite antiretroviral therapy (ART), an infection with the human immunodeficiency virus 1 (HIV-1) is still a lifelong disease because of the latent HIV reservoir. This reservoir consists of a pool of long-lived cells harbouring an integrated copy of the HIV provirus in its genome. One approach to curing HIV centres on reversing viral latency, combined with the subsequent elimination of the virus from this reservoir specifically, all while safeguarding other cells through the use of ART. This approach is colloquially known as 'shock and kill'. The limited number of latency reversing agents (LRAs) that have been studied were effective at reactivating the latent reservoir, but do not result in significant reservoir reduction (Debrabander, 2023). Investigating novel LRAs is, therefore, necessary to identify more potent ways of HIV reactivation, with the ultimate goal of reservoir depletion i.e. a functional HIV cure. The Erasmus MC HIV Eradication group has set up a translational trial platform, where successfully study the effects of novel LRAs from bench to bedside. One example is the discovery of small molecule inhibitors of BAF, which reverse HIV-1 latency, to a clinical trial investigating pyrimethamine in people living with HIV (PLWH) (Stoszko, 2016; Prins, 2023). A new promising drug target that was identified in EHEG is the glutamate receptor, ionotropic kainate 5 (GRIK5); a host factor involved in HIV latency (Roling, 2021). The registered drug topiramate was identified as a potential GRIK5 inhibitor. Further ex vivo testing confirmed HIV latency reversal of topiramate at therapeutic levels without inducing cytotoxic effects. This opens new opportunities for HIV cure research. A further knowledge gap to be explored is the influence of sex in HIV latency reversal. Typically, either by design or recruitment, male participants have been vastly overrepresented in HIV cure research (Barr, 2020). This is despite previous research showing significant difference in HIV latency reversal in women (Rao, 2022), and the importance of sex in pharmacodynamics being increasingly recognised (Gandhi, 2004; Mauvais-Jarvis, 2021). As the majority of PLWH worldwide are women and their numbers are expected to grow, studies on any potential cure strategy that provide an evidence base for their use in women increase clinical impact (UNAIDS, 2023). Therefore, the aim of this study is to examine the effect and safety of topiramate as an LRA in both men and women.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Men | Experimental | Drug: TopiramateSex assigned at birth, male Single dose of 400mg topiramate |
| Women | Experimental | Drug: TopiramateSex assigned at birth, female Single dose of 400mg topiramate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Documented HIV-1, subtype B or C
- Aged 18 or over
- On ART for a minimum of 2 consecutive years and a maximum of 12 consecutive years
- HIV-1 RNA plasma level <30 copies/mL for at least two consecutive measurements prior to inclusion (viral blips with a detectable HIVRNA 30-200 c/mL preceded and followed by HIV-RNA <30 are allowed)
- CD4+ T cell count ≥200 cells/mm^3 at screening
Key exclusion criteria (13 listed)
- Any major acute medical condition requiring hospitalisation within the past 4 weeks.
- Presence of an active opportunistic infection that defines Acquired Immunodeficiency Syndrome (AIDS).
- Any medical condition deemed by the investigator to hinder compliance with the study treatment.
- The following laboratory values at the screening phase (available before baseline (T0)): hepatic transaminases (AST or ALT) ≥3 times the upper limit of normal (ULN), serum total bilirubin ≥3 times the ULN, estimated glomerular filtration rate (eGFR) ≤60 mL/min based on CKD-EPI, haemoglobin <6.5 mmol/L (males) or <6.0 mmol/L (females), leucocytes <2.5 x10^9/L, absolute neutrophil count <1000 cells/mm^3, thrombocytes <100 x10^9/L
- Active malignancy during the past year except for basal carcinoma of the skin, stage 0 cervical carcinoma, Kaposi Sarcoma treated with ART alone, or other indolent malignancies.
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 |
|---|---|---|
| TopiramateSingle dose of 400mg | Drug | Men, Women |
Primary outcome
Effect of topiramate as measured by cell-associated HIV RNA
Time frame: 24 hours
To assess the effect of topiramate on HIV reactivation in people living with HIV on ART
Number of treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 7 days
To evaluate the clinical safety and tolerability of topiramate
2 secondary outcomes
Influence of sex on the primary outcome measures
Time frame: 24 hours
The effect of topiramate on the size of the HIV reservoir measured by relevant assays
Time frame: 24 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
- Individual participant dataSharing planned: Yes. The data will be stored in accordance with the FAIR use principle for potential future studies. If external researchers express interest in this dataset, they are encouraged to reach out to the lead investigator. Provided that sufficient privacy measures are in place, the data may be disseminated under a newly established Data Sharing Agreement.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Topiramate in people with HIV-1-infection and Hiv, run by Erasmus Medical Center at 1 site in Netherlands.
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 6 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 28 Feb 2024. 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 Netherlands. 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 combined 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.
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?
Results are not available in the source record.
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?
Effect of topiramate as measured by cell-associated HIV RNA (time frame: 24 hours). The study lists 2 primary outcomes in all. 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 28 Feb 2024.