Oral Vitamin D and Toll Like Receptor in Spondylitis Tuberculosis

NCT05376189 | Unknown Phase 2

• 1 other identifier: 0204221709
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Background : The toll-like receptor is an essential receptor that stimulates the innate immunity response. In tuberculosis, toll-like receptors, particularly the TLR-2, and TLR-4 are crucial in recognizing various ligands with a lipoprotein structure in the bacilli. Vitamin D deficiency leads to lower expression of these receptors, Hence the immune response against Mycobacterium tuberculosis will be altered. Various studies addressed the importance of vitamin D supplementation in pulmonary tuberculosis but the effect of vitamin D in extrapulmonary tuberculosis, particularly spondylitis tuberculosis is not sufficiently identified. Objectives: To assess the effect of oral vitamin D supplementation on the expression of TLR-2, TLR-4, and clinical outcomes in spondylitis tuberculosis patients. Methodology: This study proposes a randomized clinical trial of oral vitamin D supplementation in spondylitis tuberculosis patients. Multiple arms will be established with different doses and control groups. The outcome of interest includes the clinical outcomes, the expression of TLR-2, and TLR 4 Hypothesis : It is assumed that oral supplementation of Vitamin D will increase the activation of Toll-Like Receptors and improves the clinical condition of Spondylitis Tuberculosis patients

Conditions

Spondylitis; Tuberculosis

Keywords

Vitamin D; Spondylitis Tuberculosis; Clinical Improvement; Toll-Like Receptor

Outcome Measures

Primary Outcomes (4)

• The Oswestry Disability Index

  This questionnaire assess the impact of back pain to the daily life. This questionnaire contains 10 6-likert scale questions with the score ranging from 0-5 for each questions. The total score ranging from 0-50. The index is calculated as raw score per total score and presented as percentage. Below is the classification and interpretation of the score: 0% -20%: Minimal disability 21%-40%: Moderate Disability 41%-60%: Severe Disability 61%-80%: Crippling back pain 81%-100%: These patients are either bed-bound or have an exaggeration of their symptoms

  Changes of Score from Baseline to 8 weeks

• The Visual Analogue Scale

  This scale represent the pain according to a visual score measured using 10-likert scale. Maximum number indicates extreme/intractable pain

  Changes of Score from Baseline to 8 weeks

• Toll-Like Receptor 2 (TLR-2)

  The level of TLR-2 in blood measured using ELISA

  Changes of TLR-2 level from Baseline to 8 weeks

• Toll-Like Receptor 4 (TLR-2)

  The level of TLR-4 in blood measured using ELISA

  Changes of TLR-4 level from Baseline to 8 weeks

Study Arms (3)

Control Group

ACTIVE COMPARATOR

This group will be given standardized tuberculosis drug with 400 IU of oral Vitamin D3

Dietary Supplement: 400 IU; Drug: Fixed Drug Combination

Moderate Dose

EXPERIMENTAL

This group will be given standardized tuberculosis drug with 5000 IU of oral Vitamin D3

Dietary Supplement: 5000 IU; Drug: Fixed Drug Combination

High Dose

EXPERIMENTAL

This group will be given standardized tuberculosis drug with 10000 IU of oral Vitamin D3

Dietary Supplement: 10000 IU; Drug: Fixed Drug Combination

Interventions

400 IU DIETARY_SUPPLEMENT

An Oral Vitamin D3 400 IU will be given once daily for a total of 8 weeks

Also known as: Low Dose Vitamin D3

Control Group

5000 IU DIETARY_SUPPLEMENT

An Oral Vitamin D3 5000 IU will be given once daily for a total of 8 weeks

Also known as: Moderate Dose Vitamin D3

Moderate Dose

10000 IU DIETARY_SUPPLEMENT

An Oral Vitamin D3 10000 IU will be given once daily for a total of 8 weeks

Also known as: High Dose Vitamin D3

High Dose

Fixed Drug Combination DRUG

Standard Tuberculosis Regimen in a form of Fixed Drug Combination (FDC) given for Spondylitis Tuberculosis.

Also known as: Tuberculosis Regimen

Control Group; High Dose; Moderate Dose

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosed as Spondylitis Tuberculosis (Clinically and Laboratory confirmed)
• Level of Total Vitamin D \<50 nmol/L at baseline

You may not qualify if:

• Participants with pulmonary tuberculosis or other extrapulmonary tuberculosis
• Participants with osteoporosis, malignancy, cardiovascular disease, diabetes mellitus, and autoimmune disease
• Participants with liver and kidney dysfunction
• Participants who received Vitamin D prior to enrollment

Sponsors & Collaborators

• Hasanuddin University: lead

Study Sites (1)

Wahidin Sudirohusodo General Hospital

Makassar, South Sulawesi, 76124, Indonesia

Location

Related Publications (5)

• Grayling MJ, Wason JM. A web application for the design of multi-arm clinical trials. BMC Cancer. 2020 Jan 31;20(1):80. doi: 10.1186/s12885-020-6525-0.

  PMID: 32005187 BACKGROUND

• Tang L, Liu S, Bao YC, Gao RX, Han CF, Sun XC, Zhang WL, Feng SQ. Study on the relationship between vitamin D deficiency and susceptibility to spinal tuberculosis. Int J Surg. 2017 Aug;44:99-103. doi: 10.1016/j.ijsu.2017.05.077. Epub 2017 Jun 16.

  PMID: 28629765 BACKGROUND

• Panwar A, Garg RK, Malhotra HS, Jain A, Singh AK, Prakash S, Kumar N, Garg R, Mahdi AA, Verma R, Sharma PK. 25-Hydroxy Vitamin D, Vitamin D Receptor and Toll-like Receptor 2 Polymorphisms in Spinal Tuberculosis: A Case-Control Study. Medicine (Baltimore). 2016 Apr;95(17):e3418. doi: 10.1097/MD.0000000000003418.

  PMID: 27124026 BACKGROUND

• Ojaimi S, Skinner NA, Strauss BJ, Sundararajan V, Woolley I, Visvanathan K. Vitamin D deficiency impacts on expression of toll-like receptor-2 and cytokine profile: a pilot study. J Transl Med. 2013 Jul 22;11:176. doi: 10.1186/1479-5876-11-176.

  PMID: 23875738 BACKGROUND

• Yu, Fang & Cailiang, Shen. (2019). Effect of vitamin D combined with anti-tuberculosis drugs on serum IL-1β, IFN-γ and TH17 cell-associated cytokines for the management of spinal tuberculosis. Tropical Journal of Pharmaceutical Research. 18. 1141-1147. 10.4314/tjpr.v18i5.32.

  BACKGROUND

MeSH Terms

Conditions

Spondylitis; Tuberculosis

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Spinal Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Jainal Arifin, MD

  Hasanuddin University

  PRINCIPAL INVESTIGATOR

• Nasrum Massi, MD. Ph.D

  Hasanuddin University

  STUDY CHAIR

• Firdaus Hamid, MD. Ph.D

  Hasanuddin University

  PRINCIPAL INVESTIGATOR

• Andi Alfian Zainuddin, MD. Ph.D

  Hasanuddin University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jainal Arifin, MD

CONTACT

+6281144422666; ia.jenal@yahoo.co.id

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be masked from the intervention by giving a similar vitamin D preparation in each group. Investigator, Care Provider, and Outcome Assessor are blinded from allocation and only the Allocator knows the participants assigned groups
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assitant Lecturer

Model Details: This study involves three arms intervention consists of one control group with standardized tuberculosis treatment, and two intervention groups with different level of vitamin D supplementation;

Study Record Dates

• First Submitted: May 11, 2022
• First Posted: May 17, 2022
• Study Start: July 1, 2022
• Primary Completion: December 30, 2022
• Study Completion: February 1, 2023
• Last Updated: May 17, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)