Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation

Study Overview
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Brief Summary
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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.

Official Title
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Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation

Conditions
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Latent Tuberculosis, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Rifampicin 300 Mg Oral Capsule
* Drug: Isoniazid 300 Mg ORAL TABLET


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: LTBI and DM<br>Participants with LTBI and DM will be treated with Rifampicin or Isoniazid at the treating physicians discretion | Drug: Rifampicin 300 Mg Oral Capsule<br>* Rifampicin 600 mg orally once daily for 4 months<br>Drug: Isoniazid 300 Mg ORAL TABLET<br>* Isoniazid 300 mg daily for 6 months<br>|
| Other: LTBI without DM<br>Participants with LTBI without DM will be treated with Rifampicin or Isoniazid at the treating physicians discretion | Drug: Rifampicin 300 Mg Oral Capsule<br>* Rifampicin 600 mg orally once daily for 4 months<br>Drug: Isoniazid 300 Mg ORAL TABLET<br>* Isoniazid 300 mg daily for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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low-grade inflammation, glucose metabolism, body composition, cytokines, adipokines, biomarkers