## Protocol Section
### Identification Module
**NCT ID:** NCT03052179

**Acronym:** CABRIO

**Brief Title:** The Clinical and Biological Effects Of The Use Of Probiotic VSL#3 In Patients With Oral Lichen Planus

**Official Title:** The Clinical and Biological Effects Of The Use Of Probiotic VSL#3 In Patients With Oral Lichen Planus : a Proof-of-concept Study

#### Organization Study ID Info
**ID:** 16/0622
#### Organization
**Class:** OTHER
**Full Name:** University College, London
### Status Module
#### Completion Date
**Date:** 2018-09-11

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2020-03-27

**Type:** ACTUAL

**Last Update Submit Date:** 2020-03-25

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2018-09-11

**Type:** ACTUAL

#### Start Date
**Date:** 2017-08-24

**Type:** ACTUAL

**Status Verified Date:** 2020-03

#### Study First Post Date
**Date:** 2017-02-14
**Type:** ACTUAL
**Study First Submit Date:** 2017-02-09
**Study First Submit QC Date:** 2017-02-09
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University College, London

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Oral Lichen Planus (OLP) is an inflammatory disease of mucosal and skin with unknown etiology. The prevalence rate in England is reported to be between 1-2.4%. OLP contributed to around 40% of all visits or 1,200 appointments in 2014 at the Eastman Dental Hospital. Pain, discomfort, long-standing use of medications, lesion recurrence and adverse side effects of therapy are commonly associated with OLP, eventually leading to a significant reduction in a patient quality of life. In addition, there is also increased risk of developing oral cancer in patients with OLP. The current gold standard treatment for OLP is corticosteroid, which can result in adverse side effects including increased risk of infections and skin cancer, reduced systemic immune system, and hepatotoxicity with long-term usage.

Alternatively, a probiotic food supplement, VSL#3, has shown evidence of been able to induce and maintain remission in Inflammatory Bowel Disease (IBD), with no adverse effect a part than bloating, reported. Additionally, a preliminary report shown that probiotics treatment in Behcet's disease and Recurrent Aphthous Stomatitis (RAS) lesion resulted in reducing the number of oral ulcerations and subjective relief of oral discomfort.

Investigator designed a clinical trial with 30 participants allocated to one of two interventions, VSL#3 or placebo. Individuals with biopsy-confirmed OLP who experience painful symptoms will be recruited from a single site research site (Eastman Dental Hospital (EDH)). Either the active VSL#3 or the placebo, provided by Ferring Pharmaceuticals Limited, will be consume twice a day over a 30 days period. Questionnaires that will determine pain levels, disease activity and quality of life will be completed before the study begins, on days 15, 30 and 30 days after the last supplement intake. In addition saliva and blood samples will be taken before therapy begin, at 30 days of therapy, and 30 days after the last supplement intake. The levels of pro-inflammatory cytokines and the oral microbiota will be investigated using these samples. A blinded clinician will assess the clinical effects between groups of active VSL #3 and placebo and the results will analyze by statistician.

**Detailed Description:** Primary objective:

• To investigate the effects of 30 days use of supplement therapy of probiotic VSL#3 on painful symptoms of OLP at the end of the therapy (30-days endpoint) and 30 days after the last dose (60-days endpoint).

Secondary objective:

1. To investigate the effects of 30 days use of supplement therapy of probiotic VSL#3 on OLP disease activity.
2. To investigate the effect of 30 days use of supplement therapy of probiotic VSL#3 on quality of life.
3. To investigate acceptability of the intervention and potential adverse effects. and for the mechanistic study, whether :

   * The use of VSL#3 is associated with metagenomics changes in saliva.
   * The use of VSL#3 is associated with changes in the serum expression profile of pro-inflammatory cytokines.

A randomized, double blinded, placebo-controlled trial study on individuals with OLP.

Patients with painful ulcerative biopsy-confirmed OLP attending the Oral Medicine clinics of the UCLH ( University college of London hospital) Eastman Hospital and meeting the inclusion criteria of the study will be given information about the trial and invited to participate.

30 individuals who consent will be recruited and randomised in two groups: group A (15 participants) will receive the VSL#3 and group B (15 participants) will receive a placebo. A centralised computer-generated randomization list provided by an independent third party will be used to conceal allocation of patients to the treatments. The list will be sent to the drug manufacturer who will label the VSL#3 or placebo with relevant study participant code, which will come in the same identical plain-packages to ensure blinding (neither the participants nor the investigator will be aware of the sachets content). The study statistician will also be blinded to the allocation. Patients will be allowed to use best standard therapy during the study.

To demonstrate the research hypotheses, Investigators will record oral painful symptoms, disease activity, and quality of life in participants before, at 15 and 30 days from treatment start, and 30 days (day 60) after the last VSL#3 supplement intake.

60 days + 15 days 21 months Single-site 30 participants

Inclusion Criteria:

1. Biopsy-proven diagnosis of OLP as per WHO histological criteria\* with no evidence of epithelial dysplasia or malignancy.
2. Presence of painful oral symptoms associated to OLP, with minimum severity of pain being 3 or more, on a 0-10 numeric pain rating scale at screening and confirmed at recruitment/start of the intervention.
3. Age \>18 years and willing to participate into the study.
4. Receiving no therapy or receiving best standard topical therapy (typically topical corticosteroids or immunosuppressant) with the exclusion of systemic corticosteroids or systemic immunosuppressant.

   * I. R. H. Kramer, R. B. Lucas, J. J. Pindborg, and L. H. Sobin, "Definition of leukoplakia and related lesions: an aid to studies on oral precancer," Oral Surgery Oral Medicine and Oral Pathology, vol. 46, no. 4, pp. 518-539, 1978

Exclusion Criteria

1. The use of systemic antibiotics, retinoid, corticosteroids or immunosuppressant within four weeks prior to enrolment in the study.
2. Pregnancy\* or receiving IVF treatment.
3. Individuals with known history of systemic disorders affecting the immune system (e.g., connective tissue disorders, cancer, etc.)
4. Active cancer or cancer in remission undergoing maintenance with chemotherapy or immunomodulatory agents.
5. Evidence of oral epithelial dysplasia or malignancy on previous biopsy.

   * Evidence of negative pregnancy test at screening / randomization visit (strip urine test) in women of child-bearing age in which the possibility of being pregnant cannot be otherwise excluded.

### Conditions Module

**Conditions:**

- Oral Lichen Planus

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Double blind, randomized, placebo-controlled

##### Masking Info

**Masking:** DOUBLE

**Masking Description:** Either participant or the investigator will be blinded. The key of randomisation will be held by the third statistician party, and the company which supply and labeled the product study.

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** SUPPORTIVE_CARE

#### Enrollment Info

**Count:** 30

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** VSL#3 poly-biotic 450 billion in sachet orally, two sachets in the morning and two sahcets in the evening for 30 days

**Intervention Names:**

- Dietary Supplement: Poly-biotic

**Label:** VSL#3

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Maltose in sachet orally, two sachets in the morning and two sahcets in the evening for 30 days

**Intervention Names:**

- Dietary Supplement: Poly-biotic

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Placebo

- VSL#3

**Description:** Before-after treatment

**Name:** Poly-biotic

**Other Names:**

- VSL#3 5015919450087

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Other Outcomes

**Description:** To observed changing of bacterial composition before and after treatment

**Measure:** Metagenomic changing in saliva

**Time Frame:** 30 days

**Description:** To observed changing in serum level cytokine before and after treatment

**Measure:** Cytokine serum level

**Time Frame:** 30 days

#### Primary Outcomes

**Description:** is a 10 point scale for participant self-reporting pain. Participant will asked to point out the scale from 0 = no pain and 10 = worse pain can imagine.

**Measure:** pain - Numeric Rating Scale (NRS)

**Time Frame:** 30 days

#### Secondary Outcomes

**Description:** Escudier's scoring system to measure disease activity based on size and number of lesion

**Measure:** ESS

**Time Frame:** 30 days

**Description:** Validated questioner for chronic oral mucosal disease

**Measure:** COMDQ

**Time Frame:** 30 days

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Biopsy-proven diagnosis of OLP as per WHO histological criteria\* with no evidence of epithelial dysplasia or malignancy.
2. Presence of painful oral symptoms associated to OLP, with minimum severity of pain being 3 or more, on a 0-10 numeric pain rating scale at screening and confirmed at recruitment/start of the intervention.
3. Age \>18 years and willing to participate into the study.
4. Receiving no therapy or receiving best standard topical therapy (typically topical corticosteroids or immunosuppressant) with the exclusion of systemic corticosteroids or systemic immunosuppressant

Exclusion Criteria:

1. Use of systemic antibiotics, retinoid, corticosteroids or immunosuppressant.
2. Pregnancy or receiving IVF treatment.
3. Individuals with systemic disorders affecting the immune system (e.g., HIV, connective tissue disorders, cancer, etc.)
4. Evidence of oral dysplasia or malignancy on previous biopsy. -

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** London

**Country:** United Kingdom

**Facility:** University College of London Hospital

**Zip:** WC1E 6BT

#### Overall Officials

**Official 1:**

**Affiliation:** University College, London

**Name:** Andrew M Smith, Dr

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Description:** the data will be kept anynomous. This data only accessible by the party mention in the protocols

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000017512

- Term: Lichenoid Eruptions

- ID: D000017444

- Term: Skin Diseases, Papulosquamous

- ID: D000012871

- Term: Skin Diseases

- ID: D000009059

- Term: Mouth Diseases

- ID: D000009057

- Term: Stomatognathic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC07

- Name: Mouth and Tooth Diseases

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M19896

- Name: Lichen Planus, Oral

- Relevance: HIGH

- As Found: Oral Lichen Planus

- ID: M11012

- Name: Lichen Planus

- Relevance: HIGH

- As Found: Lichen Planus

- ID: M19775

- Name: Lichenoid Eruptions

- Relevance: LOW

- As Found: Unknown

- ID: M8219

- Name: Exanthema

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M19713

- Name: Skin Diseases, Papulosquamous

- Relevance: LOW

- As Found: Unknown

- ID: M12019

- Name: Mouth Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12017

- Name: Stomatognathic Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000017676

- Term: Lichen Planus, Oral

- ID: D000008010

- Term: Lichen Planus

### Misc Info Module

- Version Holder: 2024-05-24
