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

NCT03011580 | Completed Phase 2

• 1 other identifier: 011410
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Tuberculosis

Keywords

Vitamin D

Outcome Measures

Primary Outcomes (1)

• Mean maximum standardised uptake value (SUVmax) on PET-CT scanning at 8-week follow-up.

  8 weeks in total

Secondary Outcomes (10)

• Inflammation Score on PET-CT at 8-week follow-up.

  8 weeks in total

• Proportion of PET-hot lesions resolving over the course of the study

  8 weeks in total

• Total and differential white cell counts

  8 weeks in total

• Concentrations of inflammatory mediators in serum at 8-week follow-up.

  8 weeks in total

• Concentrations of inflammatory mediators in plasma at 8-week follow-up.

  8 weeks in total

Study Arms (2)

Immediate supplementation arm

EXPERIMENTAL

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

Delayed supplementation arm

PLACEBO COMPARATOR

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

Interventions

Fultium-D3 DIETARY_SUPPLEMENT

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.

Immediate supplementation arm

Placebo DIETARY_SUPPLEMENT

3 capsules of placebo will be given daily to participants in the delayed supplementation arm for 8 weeks at V2.

Delayed supplementation arm

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (1)

Barts Health NHS Trust

London, E1 1BB, United Kingdom

Location

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Adrian Martineau, Prof

  Barts and The London School of Medicine and Dentistry, Queen Mary University, University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2016
• First Posted: January 5, 2017
• Study Start: March 14, 2017
• Primary Completion: April 1, 2019
• Study Completion: August 1, 2019
• Last Updated: September 16, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)