Pulmonary Tuberculosis Patients With Diabetes Mellitus (TANDEM)

Concurrent Tuberculosis and Diabetes: Clinical Monitoring, and Microbiological and Immunological Effects of Diabetes During Tuberculosis Treatment

The purpose of this study is to evaluate the effect of enhanced glycemic monitoring of diabetes upon diabetes glycaemic control during tuberculosis treatment in tuberculosis- diabetes patients.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Pulmonary Tuberculosis
• Intervention / Treatment: Procedure: intensive monitoring

Detailed Description

Tight glycemic control may improve tuberculosis (TB) treatment outcome and help reduce symptoms. However, active TB and TB treatment hamper glycemic control. Patients starting TB treatment experience rapid changes in appetite, body composition, and inflammation (which increases insulin resistance); inflammation is a feature of untreated TB and following an increase as a result of initial bacterial killing, inflammation subsides with successful treatment. In addition, TB medication (rifampicin) increases the metabolism of oral anti-diabetic drugs including the widely used sulphonylureas and thiazolidinediones, though a possible interaction with the antidiabetic drug metformin has not been previously examined. Frequent monitoring of blood glucose with adjustments in anti-diabetes medication during the course of TB treatment may therefore be needed. However, frequent monitoring is associated with additional costs, and tools and skills for glucose monitoring and diabetes treatment may be lacking in TB or pulmonary clinics, creating a need to refer patients to other health providers. As such, a less intense schedule, preferably following the established decision points in TB treatment after 2 and 6 months would offer significant advantage. None of these issues have been addressed systematically so far.

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • West Java
    • Bandung, West Java, Indonesia, 40161
      • Faculty of Medicine, Universitas Padjadjaran
• Peru
  • San Martin De Porres
    • Lima, San Martin De Porres, Peru, 31
      • Universidad Peruana Cayetano Heredia
• Romania
  • Bucharest, Romania
    • University of Medicine and Pharmacy Craiova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult (> 18 years old) diabetes mellitus patients
• diagnosed as having active pulmonary TB
• willing to join the study

Exclusion Criteria:

• under TB treatment more than 72 hours
• steroid-induced or gestational diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intensive monitoring; more intensive monitoring strategy of blood glucose and clinical review	Procedure: intensive monitoring
No Intervention: standard monitoring; glucose monitoring followed the prevailing practice at each site

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Better diabetes control in diabetes patients with tuberculosis under treatment	Diabetes control is determined by HbA1c level (unit: %) which will be measured at month 3 and 6 of TB treatment.	Up to 6 months during TB treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost-effectiveness of different strategies for diabetes management during TB treatment	Cost analysis will include all cost for lab analysis, transportation for follow up visit, expenses for medications, all complications caused by uncontrolled diabetes (including hospitalization, medications for co morbidities)	Up to 6 months
Measurement of long-term requirements for diabetes management in TB patients diagnosed with diabetes after TB treatment completed	Clinical characteristics (i.e. blood pressure, glucose control, kidney function, quality of life (QoL) of diabetes mellitus patients with TB after completing TB treatment will be measured and will be compared between both groups.	12 months after completing TB treatment
Association between glycemic control and clinical-microbiological response to TB treatment	Association between glycemic control and clinical response to TB treatment will be determined by measuring: increasing of body weight, symptoms relieve, treatment outcome (cured, completed, failure and default), and will be compared between groups. Association between glycemic control and microbiological response to TB treatment will be determined by measuring sputum conversion time (time to negative culture), and will be compared between groups.	up to 6 months

Collaborators and Investigators

• Sponsor: Universitas Padjadjaran
• Collaborators: London School of Hygiene and Tropical Medicine; Radboud University Medical Center; University Medical Center Groningen; University of Otago; University of Stellenbosch; Leiden University Medical Center; Universidad Peruana Cayetano Heredia; St George's, University of London; University of Medicine and Pharmacy Craiova
• Investigators: Principal Investigator: Hazel Dockrell, Prof, LSHTM; Study Director: Reinout van Crevel, MD, PhD, Radboud Universisty Nijmegen Medical Center

Publications and helpful links

General Publications

• Baker MA, Harries AD, Jeon CY, Hart JE, Kapur A, Lonnroth K, Ottmani SE, Goonesekera SD, Murray MB. The impact of diabetes on tuberculosis treatment outcomes: a systematic review. BMC Med. 2011 Jul 1;9:81. doi: 10.1186/1741-7015-9-81.
• Ruslami R, Aarnoutse RE, Alisjahbana B, van der Ven AJ, van Crevel R. Implications of the global increase of diabetes for tuberculosis control and patient care. Trop Med Int Health. 2010 Nov;15(11):1289-99. doi: 10.1111/j.1365-3156.2010.02625.x.
• Bidstrup TB, Stilling N, Damkier P, Scharling B, Thomsen MS, Brosen K. Rifampicin seems to act as both an inducer and an inhibitor of the metabolism of repaglinide. Eur J Clin Pharmacol. 2004 Apr;60(2):109-14. doi: 10.1007/s00228-004-0746-z. Epub 2004 Mar 19.
• Hatorp V, Hansen KT, Thomsen MS. Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. J Clin Pharmacol. 2003 Jun;43(6):649-60.
• Jaakkola T, Backman JT, Neuvonen M, Laitila J, Neuvonen PJ. Effect of rifampicin on the pharmacokinetics of pioglitazone. Br J Clin Pharmacol. 2006 Jan;61(1):70-8. doi: 10.1111/j.1365-2125.2005.02515.x.
• Niemi M, Backman JT, Neuvonen M, Neuvonen PJ. Effect of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide in healthy subjects. Br J Clin Pharmacol. 2003 Oct;56(4):427-32. doi: 10.1046/j.1365-2125.2003.01884.x.
• Niemi M, Backman JT, Neuvonen M, Neuvonen PJ, Kivisto KT. Rifampin decreases the plasma concentrations and effects of repaglinide. Clin Pharmacol Ther. 2000 Nov;68(5):495-500. doi: 10.1067/mcp.2000.111183.
• Niemi M, Backman JT, Neuvonen M, Neuvonen PJ, Kivisto KT. Effects of rifampin on the pharmacokinetics and pharmacodynamics of glyburide and glipizide. Clin Pharmacol Ther. 2001 Jun;69(6):400-6. doi: 10.1067/mcp.2001.115822.
• Niemi M, Kivisto KT, Backman JT, Neuvonen PJ. Effect of rifampicin on the pharmacokinetics and pharmacodynamics of glimepiride. Br J Clin Pharmacol. 2000 Dec;50(6):591-5. doi: 10.1046/j.1365-2125.2000.00295.x.
• Park JY, Kim KA, Kang MH, Kim SL, Shin JG. Effect of rifampin on the pharmacokinetics of rosiglitazone in healthy subjects. Clin Pharmacol Ther. 2004 Mar;75(3):157-62. doi: 10.1016/j.clpt.2003.10.003.
• Park JY, Kim KA, Park PW, Park CW, Shin JG. Effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide. Clin Pharmacol Ther. 2003 Oct;74(4):334-40. doi: 10.1016/S0009-9236(03)00221-2.
• Syvalahti E, Pihlajamaki K, Iisalo E. Effect of tuberculostatic agents on the response of serum growth hormone and immunoreactive insulin to intravenous tolbutamide, and on the half-life of tolbutamide. Int J Clin Pharmacol Biopharm. 1976 Mar;13(2):83-9.
• Zilly W, Breimer DD, Richter E. Induction of drug metabolism in man after rifampicin treatment measured by increased hexobarbital and tolbutamide clearance. Eur J Clin Pharmacol. 1975 Dec 19;9(2-3):219-27. doi: 10.1007/BF00614021.

Helpful Links

• official website of TANDEM project

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2014
• Primary Completion (Actual): February 21, 2017
• Study Completion (Actual): December 21, 2017

Study Registration Dates

• First Submitted: March 19, 2014
• First Submitted That Met QC Criteria: April 2, 2014
• First Posted (Estimate): April 7, 2014

Study Record Updates

• Last Update Posted (Actual): April 18, 2019
• Last Update Submitted That Met QC Criteria: April 17, 2019
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: randomized controlled trial; tuberculosis; diabetes mellitus; management
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Endocrine System Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Diabetes Mellitus; Tuberculosis; Tuberculosis, Pulmonary
• Other Study ID Numbers: TB-201403.01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No