## Protocol Section
### Identification Module
**NCT ID:** NCT06420375

**Acronym:** TURTLE

**Brief Title:** Treatment of UC With Novel Therapeutics

**Official Title:** Treatment of Ulcerative Colitis With Novel Therapeutics

#### Organization Study ID Info
**ID:** Unknown (Pending approval 2.0)
#### Organization
**Class:** OTHER
**Full Name:** Brigham and Women's Hospital
### Status Module
#### Completion Date
**Date:** 2025-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-07-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-06
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Brigham and Women's Hospital

#### Responsible Party

**Investigator Affiliation:** Brigham and Women's Hospital

**Investigator Full Name:** Joshua Korzenik

**Investigator Title:** MD-Director, Brigham and Women's Hospital Crohn's and Colitis Center

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This study is a clinical trial being done to investigate the efficacy of drug BRS201 as a treatment in patients with active mild ulcerative colitis. Participation in this study will take 12 weeks long and the study is structured as a crossover study in which participants will take the study drug for 4 weeks and a placebo drug for 4 weeks in a randomized order in the form of an oral medication. Participation may also involve receiving an IV dose of the medication. The study will require participants to attend 7 study visits, all of which will be conducted at a study site. Participation will involve taking an oral medication twice daily, tracking the medication in a log, and getting blood drawn and giving a stool and urine sample for a few lab tests throughout the study.

### Conditions Module

**Conditions:**

- Ulcerative Colitis Mild

- Ulcerative Colitis

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

**Intervention Model Description:** This is a crossover study in which each participant will receive active medication for a period of time and placebo for a period of time.

##### Masking Info

**Masking:** QUADRUPLE

**Masking Description:** This is a double-blinded study.

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 18

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** In Group 1 of the study, subjects will take oral study drug at 2g twice daily, PO (4g daily) with 120mg oral butyrate twice daily (240mg daily) for 4 weeks.

In Group 2 of the study, subjects will take oral study drug at 2g twice daily, PO (4g daily) with 120mg oral butyrate twice daily (240mg daily) for 4 weeks. Subjects will also receive a one time 2.5g dose of study drug at initiation.

In Group 3 of the study, subjects will repeat the previous conditions of the group that proves to be the most effective.

**Intervention Names:**

- Drug: BRS201

**Label:** Active Comparator: BRS201 Arm

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** In Group 1 of the study, subjects will take oral placebo at 2g twice daily, PO (4g daily) with 120mg oral butyrate twice daily (240mg daily) for 4 weeks.

In Group 2 of the study, subjects will take oral placebo at 2g twice daily, PO (4g daily) with 120mg oral butyrate twice daily (240mg daily) for 4 weeks. Subjects will also receive a one time 100mg dose of cyanocobalamin at initiation.

In Group 3 of the study, subjects will repeat the previous conditions of the group that proves to be the most effective.

**Intervention Names:**

- Drug: Placebo

**Label:** Placebo Comparator: Placebo Arm

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Active Comparator: BRS201 Arm

**Description:** Groups 1, 2, and 3 will all contain 6 subjects each, with each subject receiving active study drug and placebo in a 2:1 randomized order; 4 will receive active treatment for the first for four weeks followed by placebo for four weeks, while the remaining 2 will receive placebo for four weeks followed by active treatment for four weeks.

**Name:** BRS201

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Placebo Comparator: Placebo Arm

**Description:** Groups 1, 2, and 3 will all contain 6 subjects each, with each subject receiving active study drug and placebo in a 2:1 randomized order; 4 will receive active treatment for the first for four weeks followed by placebo for four weeks, while the remaining 2 will receive placebo for four weeks followed by active treatment for four weeks.

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** The primary endpoint for this study is the capacity of study drug to normalize fecal calprotectin levels from baseline (week 0) compared to end of active treatment (4 weeks).

**Measure:** Normalization of fecal calprotectin lab measurements

**Time Frame:** 4 weeks

#### Secondary Outcomes

**Description:** Clinical symptoms assessed by SCCAI which measures patient reported outcomes on a scale of 0 to 19, where a higher score indicates more severe activity and active disease is a score of 5 or more.

**Measure:** Simple Clinical Colitis Activity Index (SCCAI)

**Time Frame:** 12 weeks

**Description:** Correlation between changes in plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin

**Measure:** Plasma nitrite, nitrate, or nitrosothiol

**Time Frame:** 8 weeks

**Description:** Reduction in fecal calprotectin to \< ULN at the end of active treatment

**Measure:** Reduction in fecal calprotectin lab measurements

**Time Frame:** 4 weeks

**Description:** Change in partial Mayo scores from baseline to end of active treatment. The partial Mayo score measures disease activity on a scale of 0 to 9, where a higher score indicates more severe disease activity and a score of 1 or less indicated remission.

**Measure:** Partial Mayo score

**Time Frame:** 4 weeks

**Description:** Analysis of urine for measurement of thiosulfate, thiocyanate, nitrate and nitrite

**Measure:** Measurement of sulfur metabolites in urine

**Time Frame:** 8 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Ability to give consent
* Patients with a confirmed diagnosis of UC for \> 3 months
* History of ≥ 15 cm of colonic involvement as confirmed by colonoscopy
* Disease activity based on calprotectin \> 200
* Allowed medications: mesalamine and sulfasalazine
* Total Mayo score of \> 5
* Patients with primary sclerosing cholangitis are eligible to enroll

Exclusion Criteria:

* History of uncontrolled hypertension with systolic BP \> 140 and systolic BP \> 90
* Chronic kidney disease as defined by GFR \<60mL/min
* Impaired hepatic function (transaminases elevated \> 2.5 x ULN) unless due to PSC
* Evidence of C. difficile (Negative test result within 1 month is acceptable)
* Infectious Colitis or drug induced colitis
* Crohn's Disease or Indeterminate colitis
* Decompensated liver disease
* Patients who are pregnant or breastfeeding
* Use of rectal therapies
* Patients who have a confirmed malignancy or cancer within 5 years
* Congenital or acquired immunodeficiencies
* Other comorbidities including: Diabetes mellitus, systemic lupus
* High likelihood of colectomy in the next 2 months
* Participation in a therapeutic clinical trial in the preceding 30 days or simultaneously during this trial
* Patients with a history or risk of cardiovascular conditions, including arrhythmia, long QT syndrome, congestive heart failure, stroke, or coronary artery disease
* Prohibited medications: Vitamin C, prednisone, immune modulators (including but not limited to azathioprine, 6-mercaptopurine, mycophenolate mofetil, tacrolimus, cyclosporine, thalidomide, interleukin-10, interleukin-11, and Omvoh or mirikizumab-mrkz) and biologics within the past six weeks including anti-TNF agents within the past six weeks, vedolizumab within the past six weeks, ustekinumab Risankizumab), a JAKi (tofacitinib or upadacitinib), or Velsipity (etrasimod) within the past 6 weeks. (The aim is to treat people who are having disease activity and just on mesalamine.)

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** jkorzenik@bwh.harvard.edu

**Name:** Joshua Korzenik, MD

**Phone:** 617 732-6389

**Role:** CONTACT

**Contact 2:**

**Email:** sellis13@bwh.harvard.edu

**Name:** Siani Ellis

**Phone:** 617-396-7703

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Chestnut Hill

**Contacts:**

***Contact 1:***

- **Email:** sellis13@bwh.harvard.edu

- **Name:** Siani Ellis

- **Phone:** 617-396-7703

- **Role:** CONTACT

***Contact 2:***

- **Email:** smitchell22@bwh.harvard.edu

- **Name:** Sophie Mitchell

- **Role:** CONTACT

***Contact 3:***

- **Name:** Joshua Korzenik, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** Brigham and Women's Hospital

**State:** Massachusetts

**Zip:** 02467

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000005759

- Term: Gastroenteritis

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000003108

- Term: Colonic Diseases

- ID: D000007410

- Term: Intestinal Diseases

- ID: D000010335

- Term: Pathologic Processes

- ID: D000015212

- Term: Inflammatory Bowel Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

### Condition Browse Module - Browse Leaves

- ID: M17206

- Name: Ulcer

- Relevance: HIGH

- As Found: Ulcerative

- ID: M6320

- Name: Colitis

- Relevance: HIGH

- As Found: Colitis

- ID: M6321

- Name: Colitis, Ulcerative

- Relevance: HIGH

- As Found: Ulcerative Colitis

- ID: M8875

- Name: Gastroenteritis

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6336

- Name: Colonic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17917

- Name: Inflammatory Bowel Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003092

- Term: Colitis

- ID: D000003093

- Term: Colitis, Ulcerative

- ID: D000014456

- Term: Ulcer

### Intervention Browse Module - Browse Branches

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: Derm

- Name: Dermatologic Agents

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M17548

- Name: Vitamin B 12

- Relevance: LOW

- As Found: Unknown

- ID: M9934

- Name: Hydroxocobalamin

- Relevance: LOW

- As Found: Unknown

- ID: M6263

- Name: Coal Tar

- Relevance: LOW

- As Found: Unknown

- ID: T451

- Name: Methylcobalamin

- Relevance: LOW

- As Found: Unknown

- ID: T476

- Name: Vitamin B12

- Relevance: LOW

- As Found: Unknown

- ID: T441

- Name: Cobalamin

- Relevance: LOW

- As Found: Unknown

- ID: T444

- Name: Cyanocobalamin

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
