Vitamin D3 to Enhance Resolution of Residual Pulmonary Inflammation in Patients Completing Antituberculosis Treatment (ResolveD-TB): a Proof-of-concept Intervention Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Mean maximum standardised uptake value (SUVmax) on PET-CT scanning at 8-week follow-up.
研究概览
简要总结
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.
详细描述
Study design and its justification:
This is an exploratory study to compare the effects of vitamin D supplementation against placebo (capsules with no active drug) on residual pulmonary inflammation detectable with PET-CT scanning. If the study demonstrates that vitamin D supplementation can dampen down lung inflammation in patients who still have such inflammation at the end of antibiotic treatment, it will provide the basis for bigger and more rigorous studies. Half of the participants will be asked to take capsules containing vitamin D (the immediate supplementation group) and the other half placebo (the delayed supplementation group) for a duration of 8 weeks, once they have completed anti-tuberculosis treatment. There is an equal chance (1 in 2) that participants will be given either study medication - this allows the two groups to be fairly similar in background characteristics so that any differences in inflammation after 8 weeks would be put down to vitamin D supplementation.
The study will adopt a 'double-blind' approach, meaning that neither participants nor researchers will know which study medication each participant is taking for the duration of the study. This allows to minimise the influence that knowing the type of study medication each participant is taking might have on researchers' or participants' behaviour during the study, as these behaviours might affect the results of the study. This is also one of the reasons that the investigators have chosen to use placebo in this study, rather than comparing participants taking vitamin D to those who are not taking any study medication. In addition, the use of placebo may encourage participants to take the study medication. It is unlikely that the delay in starting vitamin D replacement for participants in the delayed supplementation arm would be harmful, as vitamin D deficiency is very unlikely to be associated with any acute medical problem, and the delay in its correction (8 weeks) is very short in relation to the likely duration of deficiency preceding the study, which is likely to have been longstanding (e.g. over years).
Study procedures:
- Attend up to three visits to hospital after they have completed a course of antibiotics for pulmonary tuberculosis. Visit 2 may be conducted via telephone with posting of study medication (by registered mail or courier)
- Take three capsules of study medication (each is 3,200 IU so a total of 9,600 IU) every day, using the dispenser provided by the investigators
- Give two blood samples: first =19 ml (~4 tsp), second =25 ml (~5 tsp)
- Give two coughing samples
- Have two chest PET-CT scans
- Receive five telephone calls, each lasting about five minutes
- Receive additional telephone calls if any doses are missed
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Fultium-D3 (Dietary Supplement)
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.
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Mean maximum standardised uptake value (SUVmax) on PET-CT scanning at 8-week follow-up.
时间窗: 8 weeks in total
次要结局
- Total and differential white cell counts(8 weeks in total)
- Concentrations of inflammatory mediators in plasma at 8-week follow-up.(8 weeks in total)
- Concentrations of inflammatory mediators in induced sputum supernatants at 8-week follow-up.(8 weeks in total)
- Concentrations of inflammatory mediators in supernatants of antigen-stimulated whole blood at 8-week follow-up.(8 weeks in total)
- 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)
- Concentrations of inflammatory mediators in serum at 8-week follow-up.(8 weeks in total)
- Whole blood transcriptional profiles at 8-week follow-up.(8 weeks in total)
- Sputum microbiology at 8-week follow-up.(8 weeks in total)
- Induced sputum transcriptional profiles at 8-week follow-up.(8 weeks in total)