Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Latent Tuberculosis
• Intervention / Treatment: Drug: Rifampicin 300 Mg Oral Capsule; Drug: Isoniazid 300 Mg ORAL TABLET

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Niklas Lorentsson, MD; Phone Number: 31617979; Email: hans.johan.niklas.lorentsson.02@regionh.dk
• Study Contact Backup: Name: Pernille Ravn, ass.Prof; Email: pernille.ravn.02@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Herlev-Gentofte Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Herlev and Gentofte Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2021
• Primary Completion (Actual): May 1, 2023
• Study Completion (Actual): May 1, 2023

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 16, 2023
• Last Update Submitted That Met QC Criteria: May 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: biomarkers; body composition; cytokines; low-grade inflammation; glucose metabolism; adipokines
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Infections; Endocrine System Diseases; Diabetes Mellitus; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Latent Infection; Diabetes Mellitus, Type 2; Inflammation; Tuberculosis; Latent Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Fatty Acid Synthesis Inhibitors; Rifampin; Isoniazid
• Other Study ID Numbers: H-20028894 or 126496

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No