Tuberculosis Drug Levels and Continuous Glucose Monitoring in Diabetic Patients

NCT05329415 | Unknown

• 1 other identifier: v1 20.07.2021
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetes significantly increases the risk of developing active tuberculosis (TB). Diabetic patients who do develop TB have worse treatment outcomes and overall mortality. TB also worsens blood glucose control in diabetics, the mechanism of which is not well understood. The incidence of type 2 diabetes is rising globally, and consequently diabetes and TB co-infection is increasingly common, and improving outcomes in this cohort is of growing importance. Low TB drug levels in diabetic patients have been postulated as a reason for these worse outcomes. There is however contradictory evidence in the literature that TB drug levels really are consistently and significantly lower in diabetics compared with non-diabetics. If this were shown to be the case, performing therapeutic drug monitoring in diabetic patients may be a straightforward way to improve outcomes. Improving blood glucose control may also lead to improved outcomes, however there is nothing previously in the literature looking at detailed blood glucose monitoring in diabetic patients being treated for TB. This study is planned as a case control study comparing 24 non-diabetic patients commencing TB treatment with 24 cases who have both TB and diabetes. Samples for post-dose TB drug levels will be taken at 2 time points at weeks 2, 8 and 16. These will be analysed via population pharmacokinetics to compare pharmacokinetic profiles between the 2 groups, with the hypothesis that the diabetic group will have a significantly lower exposure to TB drugs than the non-diabetic group. The diabetic group will also be asked to wear a continuous glucose monitor (blinded Dexcom) for 10 days at baseline and week 16, with data compared between the 2 time points.

Conditions

Tuberculosis; Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Rifampicin/Isoniazid/Pyrazinamide Cmax 2 hours post-dose

  To be measured via population pharmacokinetic modelling, with case group compared to control group.

  2, 8, 16 weeks as discussed above

Secondary Outcomes (2)

• Antidiabetic medication Cmax at baseline and 2 hours post dose

  Baseline, 2, 8 and 16 weeks as discussed above

• Mean daily subcutaneous glucose measurement

  Baseline and 16 weeks for 10 days each

Study Arms (2)

Diabetic Group (Cases)

1. Subject aged 18 years of age or over 2. Written, informed consent obtained. 3. New diagnosis of tuberculosis and starting on anti-tuberculosis treatment 4. Known diagnosis of diabetes or a raised IFCC HbA1c level (\>= 48 mmol/mol) at the time of TB diagnosis

Diagnostic Test: TB Drug Levels

Non-Diabetic Group (Controls)

1. Subject aged 18 years of age or over 2. Written, informed consent obtained. 3. New diagnosis of tuberculosis and starting on anti-tuberculosis treatment 4. IFCC HbA1c level \< 48mmol/mol and no known diagnosis of diabetes

Diagnostic Test: TB Drug Levels

Interventions

TB Drug Levels DIAGNOSTIC_TEST

TB drug levels at 1-2 time points at weeks 2, 8 and 16

Diabetic Group (Cases); Non-Diabetic Group (Controls)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from TB clinics at London North West University NHS Trust.

You may qualify if:

• Cases:
• Subject aged 18 years of age or over
• Written, informed consent obtained.
• New diagnosis of tuberculosis and starting on anti-tuberculosis treatment
• Known diagnosis of diabetes or a raised IFCC HbA1c level (\>= 48 mmol/mol) at the time of TB diagnosis
• Controls:
• Subject aged 18 years of age or over
• Written, informed consent obtained.
• New diagnosis of tuberculosis and starting on anti-tuberculosis treatment
• IFCC HbA1c level \< 48mmol/mol and no known diagnosis of diabetes

You may not qualify if:

• Subject aged under 18 years
• Inability to give informed consent

Sponsors & Collaborators

• London North West Healthcare NHS Trust: lead

Study Sites (1)

London North West University NHS University Trust

London, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Tuberculosis; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Ann Sturdy

  LONDON NORTH WEST UNIVERSITY HEALTHCARE NHS TRUST

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2021
• First Posted: April 15, 2022
• Study Start: February 1, 2022
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2024
• Last Updated: June 7, 2023

Record last verified: 2023-04

Locations

GB (1)