Atorvastatin to Reduce Inflammation After Tuberculosis Treatment Completion

NCT04147286 | Recruiting Phase 2 DMC

• 2 other identifiers: HREC 675/2019RIA2017T-2004
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

This is a proof-of-concept phase IIB, double-blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of 40 mg atorvastatin to reduce persistent lung inflammation after successful TB treatment completion in HIV-infected and HIV-uninfected adults measured by PET/CT.

Conditions

Tuberculosis, Pulmonary

Keywords

tuberculosis; HIV; COPD; inflammation

Outcome Measures

Primary Outcomes (1)

• Total lung glycolysis (TLG) on PET/CT imaging

  The primary outcome measure is total lung glycolysis (TLG) on PET/CT imaging. Total lung glycolysis (TLG), is the total glycolytic activity (TGA) in regions of interest (both lungs). Primary outcome measurement is semi-automated using nuclear medicine medical imaging software (MIM Software Inc.). Total lung masks are drawn on every participant's PET/CT scans. Glycolytic activity is derived for each lung (SUVbw\*mL), total lung glycolytic activity is the sum of both lungs TGA.

  12 weeks

Study Arms (2)

Atorvastatin (Arm B)

ACTIVE COMPARATOR

12 weeks of 40 mg atorvastatin therapy per os daily

Drug: Atorvastatin 40mg

Placebo (Arm C)

PLACEBO COMPARATOR

Identical placebo tablet is taken per os daily

Drug: Placebo oral tablet

Interventions

Atorvastatin 40mg DRUG

12 weeks of 40 mg atorvastatin therapy per os

Atorvastatin (Arm B)

Placebo oral tablet DRUG

Identical placebo

Placebo (Arm C)

Eligibility Criteria

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

You may qualify if:

• Has completed the written informed consent process prior to undergoing any pre-screening or screening evaluations and willing to undergo HIV testing
• Age 18 to 65 years with body weight from 50 kg to 90 kg
• Clinical response to TB treatment and sputum culture negative at week 16
• Completed a 24-week course of standard TB treatment (4RHZE/2RH)
• Defined as "cured" by the TB Control Program of South Africa
• Laboratory parameters within 30 days before enrolment:
• For HIV-infected participants: receiving antiretroviral therapy for at least 12 weeks and suppressed HIV viral load within 30 days prior to enrolment
• For HIV-infected participants: CD4 counts above 350 cells/µL within 30 days prior to enrolment
• AST and ALT \<3x upper limit of normal (ULN)
• Creatinine \<2x ULN
• Hemoglobin \>7.0 g/dL
• Platelet count \>50 x109 cells/L
• Creatinine kinase \<2x ULN
• Able and willing to return to follow-up
• Willing to have samples, including DNA, stored

You may not qualify if:

• Acute illness
• Fever (temperature \>38.0 degrees centigrade)
• Participant receiving any type of lipid lowering agent at the time of screening, within three months prior to screening or likely to require any lipid lowering agent in the near future.
• Known allergy or contraindications to the investigational drug or any other statins
• Evidence of drug-resistant TB
• Extrapulmonary TB, including pleural TB and/or large pleural effusion
• Pregnant or desiring/trying to become pregnant in the next 6 months
• Unable to take oral medications
• Diabetes as defined by point of care HbA1c≥6.5, random glucose≥200mg/dL (or 11.1mmol/L), fasting plasma glucose≥126mg/dL (or 7.0mmol/L), or the presence of any anti-diabetic agent (including traditional medicines) as a concomitant medicine
• Disease complications or concomitant illnesses that may compromise safety or interpretation of trial endpoints, such as known diagnosis of chronic inflammatory condition (e.g. sarcoidosis, rheumatoid arthritis, connective tissue disorder)
• Use of immunosuppressive medications, such as TNF-alpha inhibitors or systemic or inhaled corticosteroids, within the past 2 weeks
• Use of any investigational drug in the previous 3 months
• Alcohol and substance abuse which might interfere with medication adherence during the trial
• Any person for whom the physician feels this study is not appropriate

Sponsors & Collaborators

• University of Cape Town: lead
• University of Zurich: collaborator
• University of Namibia: collaborator
• University of Bern: collaborator
• University of Stellenbosch: collaborator

Study Sites (1)

General Medicine & Global Health, Cape Heart Institute, Faculty of Health Sciences, University of Cape Town

Observatory, WC, 7925, South Africa

RECRUITING

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis; Pulmonary Disease, Chronic Obstructive; Inflammation

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Friedrich Thienemann, MD

  University of Cape Town

  PRINCIPAL INVESTIGATOR

• Reto Guler, PhD

  University of Cape Town

  STUDY CHAIR

Central Study Contacts

Friedrich Thienemann, MD

CONTACT

+27 21 406 6358; friedrich.thienemann@uct.ac.za

Sandra Mukasa, MD

CONTACT

+27 21 406 6358; sandra.mukasa@uct.ac.za

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind, randomized, placebo-controlled trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor and research group leader

Model Details: This is a proof-of-concept phase IIB, double-blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of 40 mg atorvastatin to reduce persistent lung inflammation after successful TB treatment completion in HIV-infected and HIV-uninfected adults measured by PET/CT.

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: November 1, 2019
• Study Start: July 14, 2020
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 30, 2027
• Last Updated: August 23, 2024

Record last verified: 2024-08

Locations

ZA (1)