Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation

Phase 4

Completed

• Conditions: Latent Tuberculosis; Diabetes Mellitus, Type 2
• Interventions: Drug: Rifampicin 300 Mg Oral Capsule; Drug: Isoniazid 300 Mg ORAL TABLET

• Registration Number: NCT04830462
• Lead Sponsor: Herlev and Gentofte Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-03-31
• Study First Submitted QC: 2021-03-31
• Study First Posted: 2021-04-05
• Study Start: 2021-04-15
• Status Verified: 2023-05
• Primary Completion: 2023-05-01
• Study Completion: 2023-05-01
• Last Update Submitted: 2023-05-15
• Last Update Posted: 2023-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

Inclusion criteria for the LTBIDM arm:

• 18+ years
• Known DM type 2

Inclusion criteria for LTBI arm

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

Exclusion Criteria (both arms) :

• Previous treatment for TB or LTBI
• Pregnancy
• Type 1 DM
• Known immunosuppression such as: HIV, steroid treatment within 14 days before inclusion, daily NSAID treatment, ongoing chemotherapy, ongoing immunomodulating treatment or splenectomy
• 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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LTBI and DM	Rifampicin 300 Mg Oral Capsule	Participants with LTBI and DM will be treated with Rifampicin or Isoniazid at the treating physicians discretion
LTBI without DM	Rifampicin 300 Mg Oral Capsule	Participants with LTBI without DM will be treated with Rifampicin or Isoniazid at the treating physicians discretion
LTBI and DM	Isoniazid 300 Mg ORAL TABLET	Participants with LTBI and DM will be treated with Rifampicin or Isoniazid at the treating physicians discretion
LTBI without DM	Isoniazid 300 Mg ORAL TABLET	Participants with LTBI without DM will be treated with Rifampicin or Isoniazid at the treating physicians discretion

Primary Outcome Measures

Name	Time	Method
OGTT (oral glucose tolerance test)	Time Frame: 4-6 months (depending on treatment)	Reduction in plasma glucose area under the curve during OGTT

Secondary Outcome Measures

Name	Time	Method
Changes in insulin resistance	Time Frame: 4-6 months (depending on treatment)	HOMA-IR pre and post treatment
Changes in low-grade inflammatory markers and in adipokines	Time Frame: 4-6 months (depending on treatment)	A panel of cytokines and adipokines
INF-gamma change	Time Frame: 4-6 months (depending on treatment)	Changes in IFN-γ levels after incubation with saline solution, TB antigen or phytohemagglutinin A Pre, during and post treatment
Changes in body composition	Time Frame: 4-6 months (depending on treatment)	Body composition pre and post treatment measured with DEXA-scanning and/or bioimpedance
Changes in insulin production	Time Frame: 4-6 months (depending on treatment)	Insulin/c-peptid, HOMA-B pre and post treatment

Trial Locations

Locations (1)

Herlev-Gentofte Hospital; 🇩🇰 Copenhagen, Denmark