Studying Topiramate for Re-Activating the HIV-1 Reservoir

NCT06282783 | Not Yet Recruiting Phase 1

• 1 other identifier: 2024-511532-27-00
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

HIV-1-infection; Hiv; HIV Infections; HIV I Infection

Keywords

HIV Cure; Shock and Kill; Topiramate; Latency Reversing Agents; Latency Reversal

Outcome Measures

Primary Outcomes (2)

• 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

  24 hours

• Number of treatment-related adverse events as assessed by CTCAE v4.0

  To evaluate the clinical safety and tolerability of topiramate

  7 days

Secondary Outcomes (2)

• Influence of sex on the primary outcome measures

  24 hours

• The effect of topiramate on the size of the HIV reservoir measured by relevant assays

  24 hours

Study Arms (2)

Men

EXPERIMENTAL

Sex assigned at birth, male Single dose of 400mg topiramate

Drug: Topiramate

Women

EXPERIMENTAL

Sex assigned at birth, female Single dose of 400mg topiramate

Drug: Topiramate

Interventions

Topiramate DRUG

Single dose of 400mg

Men; Women

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• CD4+ T cell count ≥200 cells/mm\^3 at screening
• Able to understand the information and give informed consent

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus Medical Centre

Rotterdam, Netherlands

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections; Shock

Interventions

Topiramate

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 12, 2024
• First Posted: February 28, 2024
• Study Start: September 1, 2024
• Primary Completion: April 1, 2025
• Study Completion: August 1, 2025
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)