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Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation

Primary Purpose

Latent Tuberculosis, Diabetes Mellitus, Type 2

Status
Completed
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Rifampicin 300 Mg Oral Capsule
Isoniazid 300 Mg ORAL TABLET
Sponsored by
Herlev and Gentofte Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Latent Tuberculosis focused on measuring low-grade inflammation, glucose metabolism, body composition, cytokines, adipokines, biomarkers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Herlev-Gentofte Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

LTBI and DM

LTBI without DM

Arm Description

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

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

Outcomes

Primary Outcome Measures

OGTT (oral glucose tolerance test)
Reduction in plasma glucose area under the curve during OGTT

Secondary Outcome Measures

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

Full Information

First Posted
March 31, 2021
Last Updated
May 15, 2023
Sponsor
Herlev and Gentofte Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04830462
Brief Title
Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation
Official Title
Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
April 15, 2021 (Actual)
Primary Completion Date
May 1, 2023 (Actual)
Study Completion Date
May 1, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Herlev and Gentofte Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Latent Tuberculosis, Diabetes Mellitus, Type 2
Keywords
low-grade inflammation, glucose metabolism, body composition, cytokines, adipokines, biomarkers

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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)
Allocation
Non-Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LTBI and DM
Arm Type
Other
Arm Description
Participants with LTBI and DM will be treated with Rifampicin or Isoniazid at the treating physicians discretion
Arm Title
LTBI without DM
Arm Type
Other
Arm Description
Participants with LTBI without DM will be treated with Rifampicin or Isoniazid at the treating physicians discretion
Intervention Type
Drug
Intervention Name(s)
Rifampicin 300 Mg Oral Capsule
Intervention Description
Rifampicin 600 mg orally once daily for 4 months
Intervention Type
Drug
Intervention Name(s)
Isoniazid 300 Mg ORAL TABLET
Intervention Description
Isoniazid 300 mg daily for 6 months
Primary Outcome Measure Information:
Title
OGTT (oral glucose tolerance test)
Description
Reduction in plasma glucose area under the curve during OGTT
Time Frame
Time Frame: 4-6 months (depending on treatment)
Secondary Outcome Measure Information:
Title
Changes in insulin production
Description
Insulin/c-peptid, HOMA-B pre and post treatment
Time Frame
Time Frame: 4-6 months (depending on treatment)
Title
Changes in insulin resistance
Description
HOMA-IR pre and post treatment
Time Frame
Time Frame: 4-6 months (depending on treatment)
Title
Changes in low-grade inflammatory markers and in adipokines
Description
A panel of cytokines and adipokines
Time Frame
Time Frame: 4-6 months (depending on treatment)
Title
INF-gamma change
Description
Changes in IFN-γ levels after incubation with saline solution, TB antigen or phytohemagglutinin A Pre, during and post treatment
Time Frame
Time Frame: 4-6 months (depending on treatment)
Title
Changes in body composition
Description
Body composition pre and post treatment measured with DEXA-scanning and/or bioimpedance
Time Frame
Time Frame: 4-6 months (depending on treatment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Herlev-Gentofte Hospital
City
Copenhagen
Country
Denmark

12. IPD Sharing Statement

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Impact of LTBI Treatment on Glucose Tolerance and Chronic Inflammation

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