Comparison of tofacitinib with NCES versus NCES alone for vitiligo
- Conditions
- Medical and Surgical, (2) ICD-10 Condition: L80||Vitiligo,
- Registration Number
- CTRI/2024/01/061532
- Lead Sponsor
- All India Institute of Medical Sciences
- Brief Summary
Patients fulfilling theinclusion criteria will be recruited after their informed written consent(Appendix 1 and 2). A detailed clinical history and examination will be done,and findings recorded in a pre-designed proforma (Appendix 3). The vitiligopatch selected for NCES will be clinically photographed using a smart phone ora hand-held camera in a well-lit room, in a uniform settingwithout magnification with standard setting of contrast and brightness. The size of the vitiligo patch will be estimated usingthe graph paper method. Dermoscopic examination of the selected vitiligo patchwill also be done and photograph taken, and findings recorded in a pre-designedproforma (Appendix 3). A 5 ml venous blood sample will be collected underaseptic precautions for complete blood count and serum biochemistry, and a Mantouxtest will be performed.
***Randomization,allocation concealment and blinding***
Patients will be randomized toreceive either tofacitinib (Group A) or placebo (Group B) using blockrandomization method with variable block size. Numbers will be prepared bycomputer generated random tables. Envelopes will be opaque and sealed with eachcontaining details of the drug. These envelopes will be made by a person notdirectly or indirectly involved in the study. One envelope will be taken perpatient and opened by one of the investigators (who is not involved inperforming NCES or evaluation of any outcome measures) and the medicine(tofacitinib or placebo) will be prescribed based on the group to which thepatient has been randomized. The patient, dermatologist performing the NCES andthe investigator evaluating the treatment response will be blinded.
4 mm skin punch biopsies willbe performed from the vitiligo patch selected for NCES and subjected to RT-PCR andELISA analysis.
***Treatment protocol***
Group A: Oral tofacitinib 5mgBD x 6 months, OD x 3 months
Group B: Oral placebo BD x 6months, OD x 3 months
*Source of drugs for the study*
Tofacitinib will be providedto the patients free of cost for the duration of study by INTAS PHARMACEUTICALS.They will not provide any financial support, and will have no role in datacollection, interpretation of results, statistical analysis, manuscriptpreparation or submission to journal for publication.
Patients in both the treatmentgroups will undergo NCES after 2 months of receiving tofacitinib or placebo. 4mm skin punch biopsy will be repeated from the vitiligo patch selected for NCESbefore the procedure, and subjected to immunofluorescence and flowcytometric analysisand RT-PCR.
Drug adverse effects will beevaluated by clinical evaluation and monitoring of complete blood count andserum biochemistry at monthly intervals for the first 3 months and then at 6months.
***Transplantation ofthe non-cultured epidermal cell suspension***
*Harvesting the graft*
About one-fourth to one-tenththe size of the recipient area will be selected as the donor site, usually onnon-cosmetically important site, like the thighs, buttocks or waist. Underaseptic precautions and EMLA (lignocaine+ prilocaine) topical anesthesia orlocal infiltration of 1% lignocaine with adrenaline, a split thickness skingraft (STSG) will be taken from donor site. The recipient site will be coveredwith a paraffin gauze, gauze piece and surgical pad and the dressing will besecured using adhesive tape.
*Preparation of NCES*
The STSG will be transportedto the laboratory in PBS in a sealed sterile centrifuge tube after properlabelling. There, the skin graft will be transferred to Trypsin-EDTA solution(0.25% trypsin and 0.05% EDTA, (Gibco BRL) in a Petri dish and incubated at37°C for 90 minutes to separate the epidermis from the dermis. After 45minutes, the trypsin– EDTA solution will be pipetted out and phosphate bufferedsaline (PBS) will be added and the tissue teased with sterile forceps so as toseparate the cells from the tissue. The solid waste of tissue will be removedand the suspension will be centrifuged at 1000 rpm for 10 minutes. Thesupernatant will then be discarded and the pellet, containing cells from thestratum basale and lower half of the stratum spinosum that are rich inmelanocytes and basal keratinocytes will be taken.
*Transplanting the NCES*
Under strict asepsis, therecipient vitiliginous areas will be anaesthetized by lignocaine 1% or topicalEMLA. It will be dermabraded using diamond burr until uniform pinpoint bleedingis noted. After that, NCES suspended in PBS will be applied and uniformlyspread. It will then be covered with dry collagen sheet, gauze piece and thensterile surgical pad. The area will be immobilized with dynaplast, and patientwill be advised to restrict movement at the site. Patients will be started on 1week course of antibiotics and anti-inflammatory agents. Dressings will beremoved after one week and patients will be asked to expose the area to sunlight10 minutes every day from 10th day onwards.
**Sample collection**
1. A5 ml of venous blood sample will be collected using the standard asepticprecautions for complete blood count, liver and renal function test and fastinglipid profile, at visits 1, 3, 4, 5, 12 and 24 (six visits). Testing for HBsAg,anti-HCV and HIV-1 and -2, and latent TB (Mantoux test) will be done only atvisit 1.
2. Aclean catch mid-stream urine sample will be collected for routine microscopy atvisit 1 only.
3. Skinpunch biopsies from the vitiligo patch selected for NCES will be taken from 10patients of tofacitinib group at the baseline (visit 1) in and 3 months (visit5) later (post-tofacitinib treatment) for analysis of mRNA expression ofvitiligo activity biomarkers (Cytokines/chemokines and receptors such as *IFN-gamma, IL15, IL-10, CXCL9, CXCL10, CCR3*etc; transcription factors such as *FOXP3,EOMES, RUNX1, GATA3, JAKs, STATs* etc) by customized PCR array (supplied byQiagen) (exploratory study).
4. Two4 mm skin punch biopsies from the vitiligo patch selected for NCES will betaken at the baseline (visit 1) in another 20 consecutive consenting patients fromeach treatment group (20 x 2 = 40) and at 3 months after receiving tofacitinibor placebo (visit 5) for analysis of mRNA expression (of target genes) and protein levels of vitiligo activity (basedon the results of PCR array) and melanogenesis (*BMP, TYR, TRP1, MITF* etc)biomarkers by RT-PCR and/or ELISA to validate the results of PCR array analysis(validation study).
Inaddition, biopsies from vitiligo (n=10) and non-vitiligo controls (n=10) willalso be taken for RT-PCR and ELISA analysis for comparison with cases.
**Outcome parameters**
***Primary outcome***
1. Proportionof patients with >80% repigmentation in the treated vitiligo patch at6 months and 1 year, in both groups
2. Meanpercentage repigmentation in the treated vitiligo patch at 6 months and 1 year,in both groups
***Secondary outcome***
1. Proportionof patients with residual ‘achromic fissure’ in the treated vitiligo patch at 6months, in both groups
2. Proportionof patients with a Vitiligo noticeability scale score of >4 in bothgroups
3. Changein the lesional skin tissue biomarkers at baseline vs post-tofacitinib primingprior to NCES (n=20 in each group)
4. Changein the lesional skin tissue biomarkers at baseline vs post-placebo primingprior to NCES (n=20 in each group)
5. Comparisonof the lesional skin tissue biomarkers post-tofacitinib priming prior to NCESvs vitiligo patches >1 year of clinical disease stability (n=10 in eachgroup)
6. Comparisonof the lesional skin tissue biomarkers post-tofacitinib priming prior to NCESvs normal skin of healthy controls (n=10 in each group)
7. Comparisonof baseline clinical and dermoscopic features in vitiligo patches with >80%repigmentation vs <80% repigmentation
8. Comparisonof sequential dermoscopic findings in vitiligo patches that showed clinicalsigns of disease reactivation at any time post NCES vs that did not
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Yet Recruiting
- Sex
- All
- Target Recruitment
- 100
Adult (>18 years) patients with non-segmental (generalized, acrofacial, focal) vitiligo clinically stable for <1 (3-12 months) year (VIDA Score +1 or +2).
1.Children, pregnant or lactating women with vitiligo 2.Patients with segmental vitiligo 3.Patients with vitiligo of clinical disease stability >1 year (VIDA score 0 or -1) 4.Patients with vitiligo of clinical disease stability < 3 months (VIDA score +3 or +4) 5.Patients with keloidal or bleeding tendency 6.Patients on topical treatment for last 2 weeks, and on phototherapy/systemic treatment for last 4 weeks 7.Patients with active tuberculosis / other systemic infection or any other contra-indication to tofacitinib 8.Patients with latent tuberculosis, who refuse prophylactic anti-tubercular treatment (Patients who have evidence of latent TB may be enrolled if they complete at least 4 weeks of appropriate treatment prior to randomization and agree to complete the remainder of treatment while in the trial) 9.Vitiligo patch <2.5cm2 or >100cm2.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1.Proportion of patients with 80% repigmentation in the treated vitiligo patch at 6 months & 1 year, in both groups 0.5, 1 year 2.Mean percentage repigmentation in the treated vitiligo patch at 6 months & 1 year, in both groups 0.5, 1 year
- Secondary Outcome Measures
Name Time Method - -
Trial Locations
- Locations (1)
AIIMS
🇮🇳South, DELHI, India
AIIMS🇮🇳South, DELHI, IndiaDr Vishal GuptaPrincipal investigator09871213543doctor.vishalgupta@gmail.com