Mucous Membrane Pemphigoid (MMP) Eye Diseases
Conditions
Interventions
This is an experimental medicine study (primary outcomes are mechanistic) with one Study Arm called the Disulfiram (DSF) Arm. Ten participants in Stage 1 will undergo a 42-day study period, incorporat
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Age
16 Years to 150 Years
Inclusion criteria
Inclusion criteria: 1. Aged =16 years 2. Persistent ocular inflammation (CCAT score =2 for >3 months) and evolving scarring 3. No change in systemic or ocular therapy for >3 months prior to enrolment, and not likely to change physician-directed standard care management over the course of the 42-day study period
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 27/09/2024: 1. Planned surgery involving the eyelid/ conjunctiva including eyelid repair surgery, oral mucosal grafting to reconstruct fornix, or tarsorrhaphy during the course of the study (surgery can be performed after the 42-day study). 2. Patients not willing to abstain or refrain from alcohol consumption 14 days pre-, during and 14 days post treatment. 3. Any history of liver disease, Or alanine transaminase (ALT) >2.5x upper limit of normal, OR bilirubin >1.5x upper limit of normal at screening. 4. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 5. Recent diagnosis of or unstable cardiac failure (within last 6 months) 6. History of cerebrovascular accidents 7. Uncontrolled hypertension 8. Known coronary artery disease 9. Recent admission to hospital related to poorly controlled diabetes (e.g. diabetic ketoacidosis or recurrent hypoglycaemic episodes requiring hospital attendance) within the last 6 months. 10. Active seasonal allergic conjunctivitis (hay fever) 11. Presence of active ophthalmic infection: bacterial, fungal or viral 12. Presence of persistent infective corneal ulcers or current eye condition impacting on the study as judged by a clinician 13. Known hypersensitivity to any of the components of the study or procedural medication 14. History of drug, medication or alcohol abuse or addiction 15. Unable to understand, speak and write the English language 16. Use of any investigational agent within 4 weeks of study entry 17. Participation in another investigational medicinal product (IMP) or ophthalmic interventional clinical trial at the same time as the present study 18. Participant has received a live attenuated vaccine within 30 days of study entry 19. Participants on an unstable dose of antidepressants or not willing to stay on the same dose throughout the study duration 20. Participants on an unstable standard daily dose of inhaled steroids or not willing to stay on the same dose throughout the study duration PRN may differ but the standard daily dose prescribed must not vary). 21. Participants who are not willing or able to adhere to study procedures and/or schedule 22. Participants with evidence of significant acute or chronic medical or psychiatric condition including severe personality disorder, suicidal risk, psychosis, or anything that, in the judgement of the investigator, would compromise the participant’s safety or ability to complete the study. 23. Participants who are currently pregnant or breast-feeding 24. Females of child-bearing potential who do not agree to use a highly effective method of birth control (plus barrier methods) during heterosexual intercourse from screening until 2 days after last study treatment 25. Females of childbearing potential using hormonal contraception for less than 3 months prior to study entry, or using hormonal contraception and not willing to stay on it for the duration of study 26. Females taking Hormone Replacement Therapy (HRT) not willing to remain on treatment for the study duration or have started HRT within the last 3 months prior to study entry or are on an unstable dose of HRT 27. Male, if not vasectomised, who does not agree to use barrier method plus a highly effective method of contraception during heterosexual intercourse from screening through to 2 days after the last dose of study treatment. Previous exclusion criteria: 1. Planned surgery involvin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response in the eye defined as a reduction in ocular surface ALDH activity by >=50%, measured in tear washings. Also, a response in the patient defined as a reduction in systematic ALDH activity by >=50% measured in serum. ALDH Activity PicoProbe™ fluorometric assay conducted on both tear washings and serum. This demonstrates disulfiram and/or active metabolite penetrates the eye and inhibits the target enzyme ALDH (measured in tear washings). NB inhibition of blood ALDH activity confirms adherence to the intervention. The difference in ALDH Activity from baseline to 14 days after treatment starts will be calculated and any eye or patient (in tear washing, serum, respectively) with at least a 50% reduction will be considered to have responded to treatment. Any eye /patient with less than a 50% reduction in activity will be considered a non-responder. To be done after all 10 patients have been recruited to stage 1 then after all 20 patients have been recruited to stage 2. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 30/12/2024: Multiple endpoints are to be evaluated during the study. The primary timepoint for comparison is day 14 compared to day 0 (baseline). In addition, multiple biological samples are taken throughout the study at defined timepoints between screening and day 28. This will allow additional analytical comparisons to be made which include all sample timepoints. 1. Inhibition of ALDH-mediated profibrotic gene expression signalling by >=50%: Polyester swabs to assess ocular surface gene expression (quantified via Nanostring fibrosis panel) and Collagen Type 1 protein expression (quantified via ELISA). Data will demonstrate normalising gene expression supportive of ocular surface and tear function (Profibrotic: COL3A1, FN1 and THBS1; Ocular surface function: SCIN, HMGS2, and XCL1/2) and Collagen Type 1 protein expression. As for the primary outcome measure, a 50% or greater reduction in the expression of genes COL3A1, FN1, and THBS1, as well as collagen type 1 protein expression will be assessed at day 14 post-treatment with the baseline levels. Previous secondary outcome measures: Multiple endpoints to be evaluated during the study. The primary timepoint for comparison is day 14 compared to day 0 (baseline). In addition, multiple biological samples are taken throughout the study at defined timepoints between screening and day 28. This will allow additional analytical comparisons to be made which include all sample timepoints. 1. Inhibition of ALDH-mediated profibrotic gene expression signalling by >=50%: Polyester swabs to assess ocular surface gene expression (quantified via Nanostring fibrosis panel) and Collagen Type 1 protein expression (quantified via ELISA). Data will demonstrate normalising gene expression supportive of ocular surface and tear function (Profibrotic: COL3A1, FN1 and THBS1; Ocular surface function: SCIN, HMGS2, and XCL1/2) and Collagen Type 1 protein expression. As for the primary outcome measure, | — |
Countries
England, United Kingdom
Contacts
Public Contact. MMP-Oral-DSF Trial office
Outcome results
None listed