Oral Vitamin D and Toll Like Receptor in Spondylitis Tuberculosis

Sponsor

Hasanuddin University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05376189

Collaborator

(none)

Enrollment

Location

Arms

7.1

Anticipated Duration (Months)

5.2

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Spondylitis Tuberculosis	Dietary Supplement: 400 IU Dietary Supplement: 5000 IU Dietary Supplement: 10000 IU Drug: Fixed Drug Combination	Phase 2/Phase 3

Detailed 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:

Toll-Like Receptors (TLR) 2 and 4 levels from the blood sample, measured using Enzyme-linked Immunoassay (ELISA).
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

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
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 :

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

Hence total sample should be 37 participants

Proposed Statistical Analysis

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

37 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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;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;

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

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

Primary Purpose:

Treatment

Official Title:

The Effect of Vitamin D Supplementation on Toll-Like Receptor (TLR) 2, 4, and Clinical Outcomes of Spondylitis Tuberculosis

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control Group This group will be given standardized tuberculosis drug with 400 IU of oral Vitamin D3	Dietary Supplement: 400 IU An Oral Vitamin D3 400 IU will be given once daily for a total of 8 weeks Other Names: Low Dose Vitamin D3 Drug: Fixed Drug Combination Standard Tuberculosis Regimen in a form of Fixed Drug Combination (FDC) given for Spondylitis Tuberculosis. Other Names: Tuberculosis Regimen
Experimental: Moderate Dose This group will be given standardized tuberculosis drug with 5000 IU of oral Vitamin D3	Dietary Supplement: 5000 IU An Oral Vitamin D3 5000 IU will be given once daily for a total of 8 weeks Other Names: Moderate Dose Vitamin D3 Drug: Fixed Drug Combination Standard Tuberculosis Regimen in a form of Fixed Drug Combination (FDC) given for Spondylitis Tuberculosis. Other Names: Tuberculosis Regimen
Experimental: High Dose This group will be given standardized tuberculosis drug with 10000 IU of oral Vitamin D3	Dietary Supplement: 10000 IU An Oral Vitamin D3 10000 IU will be given once daily for a total of 8 weeks Other Names: High Dose Vitamin D3 Drug: Fixed Drug Combination Standard Tuberculosis Regimen in a form of Fixed Drug Combination (FDC) given for Spondylitis Tuberculosis. Other Names: Tuberculosis Regimen

Arm

Intervention/Treatment

Active Comparator: Control Group

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

Dietary Supplement: 400 IU

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

Other Names:

Low Dose Vitamin D3

Drug: Fixed Drug Combination

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

Other Names:

Tuberculosis Regimen

Experimental: Moderate Dose

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

Dietary Supplement: 5000 IU

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

Other Names:

Moderate Dose Vitamin D3

Drug: Fixed Drug Combination

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

Other Names:

Tuberculosis Regimen

Experimental: High Dose

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

Dietary Supplement: 10000 IU

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

Other Names:

High Dose Vitamin D3

Drug: Fixed Drug Combination

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

Other Names:

Tuberculosis Regimen

Outcome Measures

Primary Outcome Measures

The Oswestry Disability Index [Changes of Score from Baseline to 8 weeks]
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
The Visual Analogue Scale [Changes of Score from Baseline to 8 weeks]
This scale represent the pain according to a visual score measured using 10-likert scale. Maximum number indicates extreme/intractable pain
Toll-Like Receptor 2 (TLR-2) [Changes of TLR-2 level from Baseline to 8 weeks]
The level of TLR-2 in blood measured using ELISA
Toll-Like Receptor 4 (TLR-2) [Changes of TLR-4 level from Baseline to 8 weeks]
The level of TLR-4 in blood measured using ELISA

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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