Pulmonary Tuberculosis (TB)Phase 2IRETBNCT01698476
Immune Reconstitution in Tuberculosis Disease
A Phase 2 study testing vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate) in people with Pulmonary Tuberculosis (TB), run by Karolinska Institutet at 1 site in Ethiopia.
Trial summary
The aim with study is to provide adjunctive therapy with vitamin D and phenylbutyrate together with standard anti-tuberculosis treatment to significantly improve clinical recovery among patients with untreated, active pulmonary tuberculosis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Tuberculosis (TB)
- What is being tested?
- vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 390 participants
- Where
- 1 siteEthiopia
- Study dates
- Sep 2012to Aug 2015
- Phase
- Phase 2
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV negative patients, adult patients >18 years who has not started anti-TB therapy.
- Newly diagnosed pulmonary TB confirmed by microscopy or culture but also sputum-negative clinical TB cases (defined according to the WHO 2006 criteria for sputum smear-negative TB ie. clinical symptoms of TB, chest X-ray findings and response to standard treatment).
Who cannot join
- Patients who have already started treatment with anti-TB drugs for more that 5 days.
- HIV-positive patients.
- History of anti-TB treatment in the past 2 years.
- Local extra-pulmonary TB in the absence of lung manifestations.
- Hypercalcaemia (serum calcium > 3 mmol/L) identified at baseline.
- Pregnant and breast feeding women.
- Any known liver or kidney function abnormality, malignancy or patients treated with cardiac glycosides.
Trial locations and contacts
1 site in 1 country.
Ethiopia1 site
Black Lion Hospital (BLH), Addis Ababa University, Faculty of Medicine
Addis Ababa, Lideta sub city
About this study
Official title: Immune Reconstitution in Tuberculosis Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate
The aim with study is to provide adjunctive therapy with vitamin D and phenylbutyrate together with standard anti-tuberculosis treatment to significantly improve clinical recovery among patients with untreated, active pulmonary tuberculosis.
- Conditions
- Pulmonary Tuberculosis (TB)
- Being tested
- vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate), Placebo tablets
- Keywords
- pulmonary TB, cholecalciferol, sodium phenylbutyrate, antimicrobial peptides, immune response
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)Drug
Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.
Placebo tabletsDrug
| Study group | Role | What they receive |
|---|---|---|
| vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate) | Active comparator | Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks. Receives: Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate) |
| Placebo tablets | Placebo comparator | Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks. Receives: Drug: Placebo tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite clinical TB score
A previously described composite clinical TB score will be used to monitor the efficacy of vitamin D and phenylbutyrate treatment among TB patients on standard chemotherapy. The numerical TB score will include self-reported clinical symptoms (cough, night sweats and chest pain) as well as different parameters determined upon clinical examination anemia, haemoptysis, dyspnoea, tachycardia, positive finding at lung auscultation, fever, low body mass index (BMI) and low mid upper arm circumference (MUAC). The TB score will be determined at the time of diagnosis (time point 0) and at 4, 8, 16 and 24 weeks after initiation of antimicrobial treatment with vitamin D and phenylbutyrate. The primary endpoint will be assessed at time point 8 weeks compared to baseline (time point 0).
Measured: 0 (baseline) compared to 8 weeks.
Secondary outcomes (2)
Clinical secondary endpoints
Clinical composite TB score (0, 4, 16, 24 weeks).
Modified clinical composite TB score (0, 4, 8, 16, 24 weeks).
Chest X-ray (0, 4, 8, 16, 24 weeks).
Time to sputum- and/or TB culture conversion (0, 1, 2, 3, 4, 8 weeks).
Measured: 0-4, 8, 16 and 24 weeks
Laboratory secondary endpoints
Peripheral CD4/CD8 T cell counts.
Antibodies in lymphocytes secertions (ALS) (S Ashenafi, Thorax, 2012).
Quantiferon-in-tube TB-gold (QFT).
Plasma levels of vitamin D, LL-37 and also cytokine/chemokine profiles.
Functional studies of immune cells (PBMCs).
Measured: 0, 4, 8, 16, 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2012 (estimated)
- Study startSep 2012
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Tuberculosis (TB)Studies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 390 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Addis Ababa University, Armauer Hansen Research Institute, Ethiopia
- Responsible party
- Principal investigator, Susanna Brighenti, Karolinska Institutet
- Investigators
- Susanna Brighenti, PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01698476
- Sponsor's protocol ID
- IRETB-2012
- Acronym
- IRETB
- Status last verified
- Feb 2016
- First submitted
- 25 Sep 2012
- Last updated
- 5 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bekele A, Gebreselassie N, Ashenafi S, Kassa E, Aseffa G, Amogne W, Getachew M, Aseffa A, Worku A, Raqib R, Agerberth B, Hammar U, Bergman P, Aderaye G, Andersson J, Brighenti S. Daily adjunctive therapy with vitamin D3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia. J Intern Med. 2018 Sep;284(3):292-306. doi: 10.1111/joim.12767. Epub 2018 May 23.
PubMed 29696707
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Reconstitution in Tuberculosis Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate
- ClinicalTrials.gov ID
- NCT01698476
- Acronym / sponsor ID
- IRETB / IRETB-2012
- Conditions
- Pulmonary Tuberculosis (TB)
- Keywords
- pulmonary TB, cholecalciferol, sodium phenylbutyrate, antimicrobial peptides, immune response
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 390 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Addis Ababa University, Armauer Hansen Research Institute, Ethiopia
- Study start
- Sep 2012
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 3 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim with study is to provide adjunctive therapy with vitamin D and phenylbutyrate together with standard anti-tuberculosis treatment to significantly improve clinical recovery among patients with untreated, active pulmonary tuberculosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate) | Active comparator | Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks. |
| Placebo tablets | Placebo comparator | Drug: Placebo tabletsPlacebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- HIV negative patients, adult patients >18 years who has not started anti-TB therapy.
- Newly diagnosed pulmonary TB confirmed by microscopy or culture but also sputum-negative clinical TB cases (defined according to the WHO 2006 criteria for sputum smear-negative TB ie. clinical symptoms of TB, chest X-ray findings and response to standard treatment).
Key exclusion criteria (7 listed)
- Patients who have already started treatment with anti-TB drugs for more that 5 days.
- HIV-positive patients.
- History of anti-TB treatment in the past 2 years.
- Local extra-pulmonary TB in the absence of lung manifestations.
- Hypercalcaemia (serum calcium > 3 mmol/L) identified at baseline.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks. | Drug | vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate) |
| Placebo tablets | Drug | Placebo tablets |
Primary outcome
Composite clinical TB score
Time frame: 0 (baseline) compared to 8 weeks.
A previously described composite clinical TB score will be used to monitor the efficacy of vitamin D and phenylbutyrate treatment among TB patients on standard chemotherapy. The numerical TB score will include self-reported clinical symptoms (cough, night sweats and chest pain) as well as different parameters determined upon clinical examination anemia, haemoptysis, dyspnoea, tachycardia, positive finding at lung auscultation, fever, low body mass index (BMI) and low mid upper arm circumference (MUAC). The TB score will be determined at the time of diagnosis (time point 0) and at 4, 8, 16 and 24 weeks after initiation of antimicrobial treatment with vitamin D and phenylbutyrate. The primary endpoint will be assessed at time point 8 weeks compared to baseline (time point 0).
2 secondary outcomes
Clinical secondary endpoints
Time frame: 0-4, 8, 16 and 24 weeks
Laboratory secondary endpoints
Time frame: 0, 4, 8, 16, 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2016.
- Derived from this study: PubMed 29696707Bekele A, Gebreselassie N, Ashenafi S, Kassa E, Aseffa G, Amogne W, Getachew M, Aseffa A, Worku A, Raqib R, Agerberth B, Hammar U, Bergman P, Aderaye G, Andersson J, Brighenti S. Daily adjunctive therapy with vitamin D3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia. J Intern Med. 2018 Sep;284(3):292-306. doi: 10.1111/joim.12767. Epub 2018 May 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susanna Brighenti, PhD principal investigator
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate) in people with Pulmonary Tuberculosis (TB), run by Karolinska Institutet at 1 site in Ethiopia.
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 7 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: finished, as of the sponsor's last update on 5 Feb 2016. 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 Ethiopia. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite clinical TB score (time frame: 0 (baseline) compared to 8 weeks.). 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 NCT01698476, which also lists 1 linked publication.
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 5 Feb 2016.