Spironolactone and XPB-1 Integrity in the TFIIH Complex

NCT07415811 | Enrolling By Invitation

• 1 other identifier: 61791622.6.0000.0068
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, interventional, exploratory clinical study designed to evaluate the pharmacokinetics, safety, and biological effects of spironolactone on the degradation of the XPB (ERCC3) protein and its potential impact on the HIV reservoir. Spironolactone is an FDA-approved mineralocorticoid receptor antagonist that has recently been shown in preclinical studies to induce rapid and reversible proteolytic degradation of XPB, a key subunit of the transcription factor IIH (TFIIH) complex, which is essential for cellular transcription, DNA repair, and viral replication. The study will enroll adult participants, including both HIV-negative individuals and people living with HIV receiving suppressive antiretroviral therapy with undetectable plasma viral load. Participants will receive oral spironolactone with stepwise dose escalation according to individual tolerability, followed by a post-treatment follow-up period. Primary assessments include evaluation of XPB protein degradation in CD4+ T cells and characterization of the pharmacokinetic profile of spironolactone and its active metabolites. In participants living with HIV, secondary assessments include quantitative and functional measurements of the HIV reservoir. Safety will be monitored throughout the study through clinical evaluations, laboratory testing, and electrocardiographic assessments. This study aims to generate initial clinical evidence supporting the repositioning of spironolactone as a potential component of HIV cure strategies, particularly within a "block-and-lock" approach targeting sustained viral transcriptional silencing.

Conditions

HIV

Keywords

HIV; Spironolactone; HIV Cure; XPB; Block and Lock

Outcome Measures

Primary Outcomes (1)

• XPB Protein Degradation in CD4+ T Cells

  Change in XPB (ERCC3) protein levels in peripheral blood CD4+ T cells following oral administration of spironolactone, assessed by immunoblotting and expressed as relative protein abundance compared with baseline.

  Baseline through up to 4 weeks of spironolactone treatment.

Secondary Outcomes (8)

• Peak Plasma Concentration (Cmax) of Spironolactone and Canrenone

  Baseline to Week 4 of spironolactone treatment.

• Area Under the Plasma Concentration-Time Curve (AUC) of Spironolactone and Canrenone

  Baseline to Week 4 of spironolactone treatment.

• Elimination Half-Life (t½) of Spironolactone and Canrenone

  Baseline to Week 4 of spironolactone treatment.

• Correlation Between Spironolactone/Canrenone Plasma Concentrations and XPB (ERCC3) Protein Degradation

  Baseline to Week 4 of spironolactone treatment.

• Cell-Associated HIV-1 DNA Levels in CD4+ T Cells

  Baseline to Week 4 of spironolactone treatment.

Study Arms (2)

People living with HIV (PLWH)

EXPERIMENTAL

Participants with HIV on suppressive ART will receive oral spironolactone dose escalation.

Drug: Spironolactone (drug)

People without HIV (HIV-negative)

EXPERIMENTAL

HIV-negative participants will receive the same oral spironolactone dose escalation.

Drug: Spironolactone (drug)

Interventions

Spironolactone (drug) DRUG

Oral spironolactone starting at 50 mg once daily with weekly 50 mg increments up to 400 mg/day as tolerated; dosing schedule per protocol.

Also known as: Aldactone®

People living with HIV (PLWH); People without HIV (HIV-negative)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults aged 18 to 60 years.
• Able and willing to provide written informed consent.
• For HIV-negative cohort: documented HIV-negative test result at screening.
• For HIV-positive cohort:
• documented HIV-1 infection;
• on stable antiretroviral therapy (ART); .plasma HIV-1 RNA below the limit of detection at screening.

You may not qualify if:

• Pregnancy or breastfeeding.
• Known hypersensitivity or contraindication to spironolactone.
• Clinically significant baseline electrolyte abnormalities, including hyperkalemia, or conditions that increase the risk of hyperkalemia.
• Clinically significant renal dysfunction or hepatic dysfunction that, in the investigator's judgment, increases risk with spironolactone.
• History of clinically significant cardiac arrhythmias or screening electrocardiogram findings that contraindicate spironolactone in the investigator's judgment.
• Use of aspirin (acetylsalicylic acid) on a continuous basis or recent use prior to screening, or planned use during the study.
• Current use of medications or supplements that increase potassium levels or otherwise substantially increase the risk of hyperkalemia, or inability/unwillingness to avoid high-potassium supplements and products during the intervention period.
• Use of non-steroidal anti-inflammatory drugs (NSAIDs) or systemic corticosteroids that cannot be discontinued for the duration of study drug administration.
• Any condition that, in the investigator's judgment, would interfere with study participation, study procedures, or participant safety.

Sponsors & Collaborators

• The Scripps Research Institute: collaborator
• University of Sao Paulo General Hospital: lead

Study Sites (1)

Grupo de Pesquisa Clínica em Moléstias Infecciosas

São Paulo, São Paulo, 05401000, Brazil

Location

MeSH Terms

Conditions

Bites and Stings

Interventions

Spironolactone; Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Esper G. Kallas, PhD

  University of Sao Paulo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 25, 2026
• First Posted: February 17, 2026
• Study Start: July 24, 2024
• Primary Completion: December 11, 2024
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

BR (1)