Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04428294
• Other study ID #: 126496
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: September 2020
• Est. completion date: May 2023

Study information

• Verified date: June 2020
• Source: Herlev and Gentofte Hospital
• Contact: Niklas Lorentsson, MD
• Phone: 31 61 79 79
• Email: niklas_lorentzon[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 sub-clinical 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 220
• Est. completion date: May 2023
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 inflammatory or rheumatological diseases with immune activation such as IBD, RA, Psoriasis and Wegners granulomatosis Recent antibiotic treatment (>2 days) or severe infection within 14 days before enrollment Known active cancer

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Inflammation
• Latent Tuberculosis
• Tuberculosis

Intervention

Drug:
• Rifampicin 300 Mg Oral Capsule
Rifampicin 600 mg orally once daily for 4 months
• Isoniazid 300 MG
Isoniazid 300 mg daily for 6 months

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Herlev and Gentofte Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OGTT (oral glucose tolerance test)	Reduction in plasma glucose area under the curve during OGTT	4-6 months (depending on treatment)
Secondary	Changes in insulin production	Insulin/c-peptid, HOMA-B pre and post treatment	4-6 months (depending on treatment)
Secondary	Changes in insulin resistance	HOMA-IR pre and post treatment	4-6 months (depending on treatment)
Secondary	Changes in low-grade inflammatory markers and in adipokines	A panel of cytokines and adipokes	4-6 months (depending on treatment)
Secondary	INF-gamma change	Changes in IFN-? levels after incubation with saline solution, TB antigen or phytohemagglutinin A Pre, during and post treatment	4-6 months (depending on treatment)
Secondary	Changes in body composition	Body composition pre and post treatment measured with DEXA-scanning	4-6 months (depending on treatment)