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SpondylitisPhase 2/3NCT05376189

Oral Vitamin D and Toll Like Receptor in Spondylitis Tuberculosis

A Phase 2/3 study testing 400 IU, 5000 IU and 10000 IU in people with Spondylitis and Tuberculosis, run by Hasanuddin University at 1 site in Indonesia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 to 50 years
Conditions the study is for
Spondylitis, Tuberculosis
What is being tested?
400 IU, 5000 IU and 10000 IU
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
1 siteIndonesia
Study dates
1 Jul 2022to 1 Feb 2023
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Jainal Arifin, MD contact

+6281144422666

ia.jenal@yahoo.co.id

Indonesia1 site
  • Wahidin Sudirohusodo General Hospital

    Makassar, South Sulawesi, 76124

    Jainal Arifin, MD, +628114442666, ia.jenal@yahoo.co.id

    Jainal Arifin, MD

Other trials in Indonesia

About this study

Official title: 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.

Read more

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

Read the 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.
Being tested
400 IU, 5000 IU, 10000 IU, Fixed Drug Combination
Keywords
Vitamin D, Spondylitis Tuberculosis, Clinical Improvement, Toll-Like Receptor
Medical subject headings
Spondylitis, Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 400 IUDietary supplement

    Also called Low Dose Vitamin D3

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

  • 5000 IUDietary supplement

    Also called Moderate Dose Vitamin D3

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

  • 10000 IUDietary supplement

    Also called High Dose Vitamin D3

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

  • Fixed Drug CombinationDrug

    Also called Tuberculosis Regimen

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

Study groups in NCT05376189
Study groupRoleWhat they receive
Control GroupActive comparatorThis group will be given standardized tuberculosis drug with 400 IU of oral Vitamin D3
Receives: Dietary Supplement: 400 IU; Drug: Fixed Drug Combination
Moderate DoseExperimentalThis group will be given standardized tuberculosis drug with 5000 IU of oral Vitamin D3
Receives: Dietary Supplement: 5000 IU; Drug: Fixed Drug Combination
High DoseExperimentalThis group will be given standardized tuberculosis drug with 10000 IU of oral Vitamin D3
Receives: Dietary Supplement: 10000 IU; Drug: Fixed Drug Combination

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Changes of Score from Baseline to 8 weeks

  2. 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

    Measured: Changes of Score from Baseline to 8 weeks

  3. Toll-Like Receptor 2 (TLR-2)

    The level of TLR-2 in blood measured using ELISA

    Measured: Changes of TLR-2 level from Baseline to 8 weeks

  4. Toll-Like Receptor 4 (TLR-2)

    The level of TLR-4 in blood measured using ELISA

    Measured: Changes of TLR-4 level from Baseline to 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2022
  2. Study start1 Jul 2022 (estimated)
  3. Primary completion30 Dec 2022 (estimated)
  4. Study completion1 Feb 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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;
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
37 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05376189
Sponsor's protocol ID
0204221709
Status last verified
May 2022
First submitted
11 May 2022
Last updated
17 May 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: As the data is confidential. The data sharing will be granted by investigator upon request

Publications

  • 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.

    PubMed 32005187
  • 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.

    PubMed 28629765
  • 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.

    PubMed 27124026
  • 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.

    PubMed 23875738
  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing 400 IU, 5000 IU and 10000 IU in people with Spondylitis and Tuberculosis, run by Hasanuddin University at 1 site in Indonesia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jainal Arifin, MD (+6281144422666, ia.jenal@yahoo.co.id), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Oswestry Disability Index (time frame: Changes of Score from Baseline to 8 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05376189, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2022.

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