Oral Vitamin D and Toll Like Receptor in Spondylitis Tuberculosis

May 11, 2022 updated by: Bumi Herman, Hasanuddin University

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

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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:

  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.

Study Type

Interventional

Enrollment (Anticipated)

37

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Indonesia
    • South Sulawesi
      • Makassar, South Sulawesi, Indonesia, 76124
        • Wahidin Sudirohusodo General Hospital
        • Contact:
        • Principal Investigator:
          • Jainal Arifin, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 50 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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
Drug: Fixed Drug Combination
Standard Tuberculosis Regimen in a form of Fixed Drug Combination (FDC) given for Spondylitis Tuberculosis.
Other Names:
  • Tuberculosis Regimen
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
EXPERIMENTAL: High Dose
This group will be given standardized tuberculosis drug with 10000 IU of oral 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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Oswestry Disability Index
Time Frame: 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
Changes of Score from Baseline to 8 weeks
The Visual Analogue Scale
Time Frame: 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
Changes of Score from Baseline to 8 weeks
Toll-Like Receptor 2 (TLR-2)
Time Frame: Changes of TLR-2 level from Baseline to 8 weeks
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)
Time Frame: Changes of TLR-4 level from Baseline to 8 weeks
The level of TLR-4 in blood measured using ELISA
Changes of TLR-4 level from Baseline to 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hasanuddin University

Investigators

  • Principal Investigator: Jainal Arifin, MD, Hasanuddin University
  • Study Chair: Nasrum Massi, MD. Ph.D, Hasanuddin University
  • Principal Investigator: Andi Alfian Zainuddin, MD. Ph.D, Hasanuddin University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

July 1, 2022

Primary Completion (ANTICIPATED)

December 30, 2022

Study Completion (ANTICIPATED)

February 1, 2023

Study Registration Dates

First Submitted

May 11, 2022

First Submitted That Met QC Criteria

May 11, 2022

First Posted (ACTUAL)

May 17, 2022

Study Record Updates

Last Update Posted (ACTUAL)

May 17, 2022

Last Update Submitted That Met QC Criteria

May 11, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0204221709

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

As the data is confidential. The data sharing will be granted by investigator upon request

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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