Oral Vitamin D and Toll Like Receptor in Spondylitis Tuberculosis

Hasanuddin University

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Tuberculosis; Spondylitis

Treatments: Dietary Supplement: 400 IU; Drug: Fixed Drug Combination; Dietary Supplement: 5000 IU; Dietary Supplement: 10000 IU

Study type: Interventional

Funder types: Other

Identifiers

NCT05376189

0204221709

Details and patient eligibility

About

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

Full description

Target population:

Patients with spondylitis tuberculosis without the involvement of lung and other extrapulmonary infection

Design:

Randomized Clinical Trial with 3 arms

Primary Intervention:

Standardized Tuberculosis treatment with oral Vitamin D3 Supplementation daily for 8 weeks

Outcome:

1. Toll-Like Receptors (TLR) 2 and 4 levels from the blood sample, measured using Enzyme-linked Immunoassay (ELISA).
2. Clinical Evaluation with Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI).

The outcomes will be measured three times at 4-week intervals (baseline, week 4, and week 8)

Sample Size and Recruitment Participants will be recruited from hospitals and allocated by simple randomization

Biological Sample and consent

1. Participants are aware that clinical data collection and biological samples will be obtained by researchers. This is mentioned in informed consent prior to study recruitment
2. Blood sample will be obtained in a standardized phlebotomy procedure and will not be retained after the study is finish.

Hypothesis Sample Size Calculation:

The trial will be designed to compare 2 experimental treatments to a shared control arm.

The sample size was estimated based on the mathematical calculation by a study below Grayling, M.J et al

With the assumption of :

1. K=2 experimental treatments will be included in the trial.
2. A significance level of α=0.05 will be used, in combination with no multiple comparison correction.
3. The event rate in the control arm will be assumed to be: λ0=5.
4. The marginal power for each null hypothesis will be controlled to level 1-β=0.8 under each of their respective least favorable configurations.
5. The interesting and uninteresting treatment effects will be δ1=2.5 and δ0=0 respectively.
6. The target allocation to each of the experimental arms will be the same as the control arm.
7. The sample size in each arm will not be required to be an integer.

Hence total sample should be 37 participants

Proposed Statistical Analysis

1. Descriptive Statistics
2. Bivariate Analysis
3. The study will apply intention-to-treat analysis
4. Linear Mixed model to measure the effect of intervention adjusted by fixed and random factors.

Enrollment: 37 estimated patients

Sex: All

Ages: 19 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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37 participants in 3 patient groups

Control Group

Active Comparator group

Description:

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

Treatment:

Drug: Fixed Drug Combination

Dietary Supplement: 400 IU

Moderate Dose

Experimental group

Description:

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

Treatment:

Drug: Fixed Drug Combination

Dietary Supplement: 5000 IU

High Dose

Experimental group

Description:

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

Treatment:

Dietary Supplement: 10000 IU

Drug: Fixed Drug Combination