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Vitamin D to Resolve Inflammation After Tuberculosis (ResolveD-TB) (ResolveD-TB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03011580
Recruitment Status : Completed
First Posted : January 5, 2017
Last Update Posted : September 16, 2019
Sponsor:
Information provided by (Responsible Party):
Queen Mary University of London

Brief Summary:

This Strategic Research Project is a translational proof-of-concept study that will determine whether vitamin D3 has potential to prevent recurrent tuberculosis (TB), as indicated by enhanced resolution of pulmonary inflammation detected using 18F-FDG PET-CT scanning. The extent of pulmonary inflammation detectable on PET-CT scanning is a validated biomarker that has previously been shown to predict risk of TB recurrence in patients taking anti-TB treatment. The investigators propose to explore whether vitamin D3 can enhance resolution of PET-CT-detectable pulmonary inflammation, on the basis of extensive preliminary data from in vitro studies and a Phase 2b clinical trial that the investigators have conducted, showing that high-dose vitamin D3 accelerates resolution of peripheral blood inflammatory responses in patients with pulmonary TB.

Forty vitamin D-deficient patients who have completed 6 months' TB treatment, but who still have residual pulmonary inflammation detectable on PET-CT scanning, will be allocated to receive either an 8-week course of high-dose oral vitamin D3 supplementation or placebo during the study period. The extent of pulmonary inflammation on PET-CT scanning will be compared between intervention vs. control groups at 8-week follow-up.

If the study shows a positive result, it will generate valuable proof-of-concept data that could be used to support an application to conduct a large phase 3 trial of vitamin D supplementation to prevent TB recurrence.


Condition or disease Intervention/treatment Phase
Recurrent Tuberculosis Dietary Supplement: Fultium-D3 Dietary Supplement: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Vitamin D3 to Enhance Resolution of Residual Pulmonary Inflammation in Patients Completing Antituberculosis Treatment (ResolveD-TB): a Proof-of-concept Intervention Study
Actual Study Start Date : March 14, 2017
Actual Primary Completion Date : April 1, 2019
Actual Study Completion Date : August 1, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Vitamin D

Arm Intervention/treatment
Experimental: Immediate supplementation arm

Fultium-D3 (oral cholecalciferol or vitamin D3) will be given at a dose of 9,600 IU/day for 8 weeks (three capsules once daily as each Fulitium D-3 capsules contains 3,200 IU vitamin D3). Participants may also be given a Sensemedic dispenser each for real-time adherence monitoring and shown how to use it.

All participants will be given a supply of Fultium-D3 at a dose of 3,200 IU/day at the end of the study.

Dietary Supplement: Fultium-D3
Fultium-D3 (oral cholecalciferol or vitamin D3) will be given to participants in the immediate supplementation arm at a dose of 9,600 IU/day for 8 weeks at V2. At V3, all participants will be given a supply of Fultium-D3 at a dose of 3,200 IU/day.

Placebo Comparator: Delayed supplementation arm
Oral placebo will be given for 8 weeks at a dose of three capsules once daily. Fultium-D3 and placebo will be identical in appearance and taste. Participants may also be given a Sensemedic dispenser each for real-time adherence monitoring and shown how to use it. All participants will be given a supply of Fultium-D3 at a dose of 3,200 IU/day at the end of the study.
Dietary Supplement: Placebo
3 capsules of placebo will be given daily to participants in the delayed supplementation arm for 8 weeks at V2.




Primary Outcome Measures :
  1. Mean maximum standardised uptake value (SUVmax) on PET-CT scanning at 8-week follow-up. [ Time Frame: 8 weeks in total ]

Secondary Outcome Measures :
  1. Inflammation Score on PET-CT at 8-week follow-up. [ Time Frame: 8 weeks in total ]
    A single composite outcome score derived from the following components: total glycolytic activity, total cavitary air, total volume of lesions with radiodensity ranging from -100 to +200 Houndsfield Units

  2. Proportion of PET-hot lesions resolving over the course of the study [ Time Frame: 8 weeks in total ]
  3. Total and differential white cell counts [ Time Frame: 8 weeks in total ]
  4. Concentrations of inflammatory mediators in serum at 8-week follow-up. [ Time Frame: 8 weeks in total ]
  5. Concentrations of inflammatory mediators in plasma at 8-week follow-up. [ Time Frame: 8 weeks in total ]
  6. Concentrations of inflammatory mediators in induced sputum supernatants at 8-week follow-up. [ Time Frame: 8 weeks in total ]
  7. Concentrations of inflammatory mediators in supernatants of antigen-stimulated whole blood at 8-week follow-up. [ Time Frame: 8 weeks in total ]
  8. Induced sputum transcriptional profiles at 8-week follow-up. [ Time Frame: 8 weeks in total ]
  9. Whole blood transcriptional profiles at 8-week follow-up. [ Time Frame: 8 weeks in total ]
  10. Sputum microbiology at 8-week follow-up. [ Time Frame: 8 weeks in total ]
    To assess the proportion of samples in which Mycobacterium tuberculosis can be detected after 8 weeks.



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 20 years or more at enrolment
  • Baseline serum 25-hydroxyvitamin D <50 nmol/L
  • Maximum standardised uptake value (SUVmax) on baseline PET-CT ≥3 g/ml
  • Completing antimicrobial therapy for pulmonary tuberculosis
  • If a woman of child-bearing potential, has negative pregnancy test immediately prior to each PET-CT scan and agrees to use reliable form of contraception until she has completed the study
  • Gives written informed consent to participate

Exclusion Criteria:

  • Pregnant, breastfeeding or planning a pregnancy
  • Baseline serum corrected calcium concentration ≥2.65 mmol/L
  • Baseline eGFR ≤ 30 ml/min/1.73 m2
  • Other contra-indication to vitamin D supplementation: known sarcoidosis, known hyperparathyroidism or known nephrolithiasis
  • Taking concomitant phenytoin, barbiturate, cardiac glycoside, oral glucocorticoid or vitamin D supplement
  • Known allergy to vitamin D or its excipients
  • Currently taking part in another interventional research study
  • PET-CT scan within the previous 6 months
  • Any inclusion criteria not met

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03011580


Locations
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United Kingdom
Barts Health NHS Trust
London, United Kingdom, E1 1BB
Sponsors and Collaborators
Queen Mary University of London
Investigators
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Principal Investigator: Adrian Martineau, Prof Barts and The London School of Medicine and Dentistry, Queen Mary University, University of London
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Responsible Party: Queen Mary University of London
ClinicalTrials.gov Identifier: NCT03011580    
Other Study ID Numbers: 011410
First Posted: January 5, 2017    Key Record Dates
Last Update Posted: September 16, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No individual participant data will be available. Non-patient identifiable data will be presented in paper, abstract and presentation to conferences.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Queen Mary University of London:
Vitamin D
Additional relevant MeSH terms:
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Tuberculosis
Inflammation
Pathologic Processes
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections