Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation

NCT04830462 | Completed Phase 4

• 1 other identifier: H-20028894 or 126496
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be investigating the effect of latent tuberculosis infection (LTBI) treatment on glucose tolerance and low-grade inflammation. Almost a century ago, researchers proposed that diabetes (DM) was associated with increased risk of Tuberculosis infection (TB). A more recent systematic review concluded that DM increases the relative risk for TB 3.1 times. Reversely, TB may affect the glycaemic control; TB is in many cases a chronic infection characterised by long term low-grade inflammation and weight loss, and persons with TB are known to be at risk of hyperglycaemia and DM at time of diagnosis. A latent infection with the m.tuberculosis bacteria is "silent" without symptoms. 1,7 billion have LTBI on a global scale. Event though the infected person does not experience symptoms, increased background inflammation has been shown in LTBI patients in previous studies. We also know that an increase in inflammatory markers precedes clinical development of DM, and that subclinical inflammation contributes to insulin resistance. We hypothesise that LTBI contributes to dysregulated glucose metabolism due to increased low-grade inflammation, and that treatment will reduce low-grade inflammation and improve glucose tolerance.

Conditions

Latent Tuberculosis; Diabetes Mellitus, Type 2

Keywords

low-grade inflammation; glucose metabolism; body composition; cytokines; adipokines; biomarkers

Outcome Measures

Primary Outcomes (1)

• OGTT (oral glucose tolerance test)

  Reduction in plasma glucose area under the curve during OGTT

  Time Frame: 4-6 months (depending on treatment)

Secondary Outcomes (5)

• Changes in insulin production

  Time Frame: 4-6 months (depending on treatment)

• Changes in insulin resistance

  Time Frame: 4-6 months (depending on treatment)

• Changes in low-grade inflammatory markers and in adipokines

  Time Frame: 4-6 months (depending on treatment)

• INF-gamma change

  Time Frame: 4-6 months (depending on treatment)

• Changes in body composition

  Time Frame: 4-6 months (depending on treatment)

Study Arms (2)

LTBI and DM

OTHER

Participants with LTBI and DM will be treated with Rifampicin or Isoniazid at the treating physicians discretion

Drug: Rifampicin 300 Mg Oral Capsule; Drug: Isoniazid 300 Mg ORAL TABLET

LTBI without DM

OTHER

Participants with LTBI without DM will be treated with Rifampicin or Isoniazid at the treating physicians discretion

Drug: Rifampicin 300 Mg Oral Capsule; Drug: Isoniazid 300 Mg ORAL TABLET

Interventions

Rifampicin 300 Mg Oral Capsule DRUG

Rifampicin 600 mg orally once daily for 4 months

LTBI and DM; LTBI without DM

Isoniazid 300 Mg ORAL TABLET DRUG

Isoniazid 300 mg daily for 6 months

LTBI and DM; LTBI without DM

Eligibility Criteria

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

You may qualify if:

• + years
• Known DM type 2
• + years
• LTBI positive
• No diagnosis with or known DM (1 and 2)

You may not qualify if:

• Previous treatment for TB or LTBI
• Pregnancy
• Type 1 DM
• Known contraindication to both study drugs
• Known active liver disease
• Known severe inflammatory or rheumatological diseases with immune activation and need for prolonged systemic treatment such as IBD, RA, Psoriasis and Wegners granulomatosis
• Recent antibiotic treatment (\>2 days) or severe infection within 14 days before enrollment
• Known active cancer

Sponsors & Collaborators

• Herlev and Gentofte Hospital: lead

Study Sites (1)

Herlev-Gentofte Hospital

Copenhagen, Denmark

Location

Related Publications (2)

• Lorentsson HJN, Clausen CR, Faurholt-Jepsen D, Hansen KB, Ritz C, Jensen SG, Rasmussen EM, Jorgensen A, Lillebaek T, Knop F, Ravn P. The impact of an oral glucose load on IFN-gamma-release in persons infected with Mycobacterium tuberculosis. BMC Infect Dis. 2024 Sep 30;24(1):1079. doi: 10.1186/s12879-024-09920-x.

  PMID: 39350021 DERIVED

• Lorentsson HJN, Clausen CR, Faurholt-Jepsen D, Hansen KB, Jensen SG, Krogh-Madsen R, Hagelqvist PG, Johansson PI, Vilsboll T, Knop FK, Ravn P. The effect of Mycobacterium tuberculosis treatment on thrombelastography-assessed haemostasis: a prospective cohort study. Thromb J. 2024 Jun 26;22(1):54. doi: 10.1186/s12959-024-00625-4.

  PMID: 38918780 DERIVED

MeSH Terms

Conditions

Latent Tuberculosis; Diabetes Mellitus, Type 2

Interventions

Rifampin; Isoniazid; Tablets

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: The study consists of two arms with different patient populations. Both arms will receive identical treatment. Arm A will have type 2 diabetes and latent tuberculosis infection (LTBI). Group B will not have any form of diabetes, but LTBI.

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: April 5, 2021
• Study Start: April 15, 2021
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: May 16, 2023

Record last verified: 2023-05

Locations

DK (1)