Clinical trial NCT00857402: Arginine as an Adjuvant Treatment Against Tuberculosis
Official title: Arginine Rich Food Supplementation as an Adjuvant Treatment Against Tuberculosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tuberculosis
HIV
Keywords: Arginine
Nitric oxide
Peanuts
Sedimentation rate
Lead sponsor: Linkoeping University
Sponsor class: OTHER_GOV
Collaborators: name: University of Gondar
name: Kalmar County Hospital
First posted: 2009-03-06
Enrollment: 180
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study was to investigate if adjuvant treatment with arginine (the substrate for nitric oxide production) rich food supplements could improve clinical outcome in patients with smear positive tuberculosis by affecting nitric oxide production.

Detailed description: Tuberculosis (TB) is disease of increased global public health importance. Because of emerging multi drug resistance and the long treatment duration there is a need to optimize the current chemotherapy. Host immunity is important in determining the susceptibility and outcome of disease as could be exemplified by co infection with HIV which dramatically increases the risk to develop TB.

Previous results from our group and others show that nitric oxide produced by activated macrophages from arginine might be important to control the disease. However, the relative importance of nitric oxide in human TB has been debated. In a previous study in Gondar, Ethiopia, we observed an effect of adjuvant treatment with arginine capsules on sputum smear conversion and reduction of cough. In this study we wanted to test the hypothesis based on previous observations that an arginine rich food supplementation might enhance clinical improvement in patients with smear positive tuberculosis and if this effect could be due to increased nitric oxide production.

Eligibility criteria: Inclusion Criteria:

* Informed and written consent to take part in the study
* Previously untreated and newly diagnosed smear positive Tb patients according to the WHO definitions

Exclusion Criteria:

* Hospitalization
* Pregnancy
* Known allergy against peanuts
* Chronic or acute disease other than tuberculosis/HIV

Primary outcomes:
measure: Final outcome according to WHO
timeFrame: 8 months
Secondary outcomes:
measure: Change in Chest X-ray pattern from baseline to 2 months
timeFrame: 2 months
measure: Levels of exhaled and urinary nitric oxide
timeFrame: First week, week 2, week 8, and month 5
measure: Weight gain from baseline until 2 months
timeFrame: 2 months
measure: Sedimentation rate
timeFrame: 2 months
measure: Sputum smear conversion
timeFrame: 2 months
measure: Reduction of cough from baseline to 2 months
timeFrame: 1 and 2 months
Other outcomes:
Locations:
city: Gondar, Region 3, Ethiopia
country: Ethiopia
facility: Gondar University, DOTS-center
state: Gondar
Study officials:
affiliation: Linkoeping University
name: Thomas Schön, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Sven Britton, Professor
role: STUDY_DIRECTOR
affiliation: Linkoeping University, Sweden
name: Tommy Sundqvist, Professor
role: STUDY_CHAIR
References:
citation: Schon T, Wolday D, Elias D, Melese E, Moges F, Tessema T, Stendahl O, Sundqvist T, Britton S. Kinetics of sedimentation rate, viral load and TNF-alpha in relation to HIV co-infection in tuberculosis. Trans R Soc Trop Med Hyg. 2006 May;100(5):483-8. doi: 10.1016/j.trstmh.2005.07.018. Epub 2005 Oct 20.
citation: Schon T, Elias D, Moges F, Melese E, Tessema T, Stendahl O, Britton S, Sundqvist T. Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis. Eur Respir J. 2003 Mar;21(3):483-8. doi: 10.1183/09031936.03.00090702.
citation: Wang CH, Liu CY, Lin HC, Yu CT, Chung KF, Kuo HP. Increased exhaled nitric oxide in active pulmonary tuberculosis due to inducible NO synthase upregulation in alveolar macrophages. Eur Respir J. 1998 Apr;11(4):809-15. doi: 10.1183/09031936.98.11040809.
citation: Idh J, Westman A, Elias D, Moges F, Getachew A, Gelaw A, Sundqvist T, Forslund T, Alemu A, Ayele B, Diro E, Melese E, Wondmikun Y, Britton S, Stendahl O, Schon T. Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection. BMC Infect Dis. 2008 Oct 24;8:146. doi: 10.1186/1471-2334-8-146.
citation: Schon T, Idh J, Westman A, Elias D, Abate E, Diro E, Moges F, Kassu A, Ayele B, Forslund T, Getachew A, Britton S, Stendahl O, Sundqvist T. Effects of a food supplement rich in arginine in patients with smear positive pulmonary tuberculosis--a randomised trial. Tuberculosis (Edinb). 2011 Sep;91(5):370-7. doi: 10.1016/j.tube.2011.06.002. Epub 2011 Aug 2.