## Protocol Section
### Identification Module
**NCT ID:** NCT06421818

**Brief Title:** Effect and Mechanism of Baitouweng Decoction for Large Intestine Damp-heat Syndrome of Ulcerative Colitis

**Official Title:** Formula-to-Syndrome Effect and Pharmacomicrobiomics Mechanism of Colon Delivery of Baitouweng Decoction for Treating Large Intestine Damp-heat Syndrome of Ulcerative Colitis

#### Organization Study ID Info
**ID:** BTW-RCT
#### Organization
**Class:** OTHER
**Full Name:** The Second Hospital of Nanjing Medical University
### Status Module
#### Completion Date
**Date:** 2026-12-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-21

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2026-12-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

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

#### Collaborators

**Class:** OTHER

**Name:** Heilongjiang University of Chinese Medicine

#### Lead Sponsor

**Class:** OTHER

**Name:** The Second Hospital of Nanjing Medical University

#### Responsible Party

**Investigator Affiliation:** The Second Hospital of Nanjing Medical University

**Investigator Full Name:** Faming Zhang

**Investigator Title:** chief physician, PhD

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Baitouweng Decoction is traditionally used to treat large intestine damp-heat syndrome of ulcerative colitis (UC) by oral administration and rectal enema.The project applicant's invention of transendoscopic entral tubing (TET) has been used in Baitouweng Decoction for the treatment of UC across the whole colon, however, the efficacy have not been reported and the underlying mechanism is still unclear. Compared with oral and rectal enema, Baitouweng Decoction by colon TET can improve the therapeutic effect by increasing the concentration of drugs in the whole colon, which need to be verified. This project will reveal the prescription effect and drug-microbiome interaction mechanism of whole colon repeated administration of Baitouweng Decoction in the treatment of UC through clinical randomized controlled studies, deep intestinal dynamic sampling, integrated analysis of multi-omics and TCM prescription metabolomics studies, and provide key scientific basis for the establishment of a new approach of whole colon repeated administration of TCM and a new strategy for the treatment of UC.

**Detailed Description:** A multi-center randomized controlled study will be conducted to compare the efficacy differences and multi-omics changes of colon TET, rectal enema and oral Baitouweng Decoction in the control of intestine damp-heat syndrome of UC. Moreover，a group of patients was designed to receive blank carrier solution through colon TET tube. After the study, the patients in this group were given compensation treatment of fecal microbiota transplantation as an ethical protection measure.The colonic TET will be implanted into the intestine and the whole colon will be covered with Baitouweng Decoction. The treatment period is 10 days. The primary outcome measure is the changes of fecal calprotectin before and after oral, colonic TET and rectal enema administration. And the secondary outcomes measure are the changes of disease condition, Mayo score and safety. Deep intestine fluid, stool, blood and urine samples were collected before and after treatment to study the changes of microbiomes, metabolomics and immunoomics. Identify the difference of the key material basis of Baitouweng Decoction and analyze its mechanism comprehensively. The key beneficial and harmful bacteria were identified by comprehensive analysis. A total of not less than 144 subjects are expected to be included and divided into colonic TET treatment group, colonic TET placebo group, rectal enema group, and oral group according to a ratio of 1:1:1:1.

### Conditions Module

**Conditions:**

- Ulcerative Colitis

**Keywords:**

- Baitouweng Decoction

- Formula-to-Syndrome Effect

- Ulcerative colitis

- Pharmacomicrobiomics

- Colon delivery

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Masking Description:** For groups receiving Baitouweng Decoction by oral administration and rectal edema，the interventions are single-blind to investigators and outcomes assessor. For groups receiving Baitouweng Decoction or placebo by colonic TET, the interventions are double-blind to participants, care provider, investigators and outcomes assessor.

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 144

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Baitouweng Decoction is administered through the colonic TET.

**Intervention Names:**

- Drug: Baitouweng Tang

**Label:** Colonic TET treatment group

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** The same volume of placebo as the colonic TET treatment group was administered through the colonic TET.

**Intervention Names:**

- Other: Placebo

**Label:** Colonic TET placebo group

**Type:** PLACEBO_COMPARATOR

#### Arm Group 3

**Description:** Baitouweng Decoction is administered through rectal enema.

**Intervention Names:**

- Drug: Baitouweng Tang

**Label:** Rectal enema group

**Type:** ACTIVE_COMPARATOR

#### Arm Group 4

**Description:** Baitouweng Decoction is administered through oral.

**Intervention Names:**

- Drug: Baitouweng Tang

**Label:** Oral group

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Colonic TET treatment group

- Oral group

- Rectal enema group

**Description:** Baitouweng Decoction is composed of four herbs: Baitouweng, Rhizoma coptidis, Phellodendri huangbai and Qin Pi.

**Name:** Baitouweng Tang

**Other Names:**

- Baitouweng Decoction

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Colonic TET placebo group

**Description:** The same volume and color as Baitouweng Decoction.

**Name:** Placebo

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** To compare the concentration of fecal calprotecin before and after oral, colonic TET and rectal enema administration.

**Measure:** The concentration of fecal calprotecin.

**Time Frame:** Baseline; Day 15; Day 53

#### Secondary Outcomes

**Description:** To compare the change of Mayo score before and after oral, colonic TET and rectal enema administration. The Mayo score included the number of bowel movements, blood in the stool, endoscopic findings and overall physician evaluation. The total score was 12 points. The higher the score, the higher the degree of disease activity.

**Measure:** The change of Mayo score.

**Time Frame:** Baseline; Day 15; Day 22; Day 53; Day 99.

**Description:** The number of adverse reactions that are associated with Baitouweng Decoction reported by subjects from the start of treatment to the end of follow-up.

**Measure:** Incidence of Treatment-Emergent Adverse Events

**Time Frame:** Day 15; Day 22; Day 53; Day 99.

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Patients diagnosed with ulcerative colitis;
2. The patients are in mild to moderate active stage with Mayo score of 3-8.
3. Patients with damp-heat syndrome of large intestine according to TCM syndrome differentiation: according to the expert consensus on integrated traditional Chinese and Western medicine diagnosis and treatment of UC, the main symptoms are diarrhea, mucopurulent and bloody stool, abdominal pain, and tenesmus. Secondary symptoms: anal burning, body heat is not Yang, dry mouth and bitter mouth, short red urine. Tongue pulse: tongue red fur yellow greasy, pulse slippery number. The determination of the above 8 syndromes can be made if there are 2 main symptoms and 1-2 secondary symptoms. The tongue pulse is for reference only.
4. The patients who can tolerate Baitouweng Decoction;
5. The patients who tolerance to colonoscopy and TET;
6. The patients who know and agree to participate in the clinical trial.

Exclusion Criteria:

1. The patients are complicated with other diseases that may cause diarrhea, such as infectious colitis, radiation enteritis, Crohn's disease, etc.
2. Patients with heart, brain, lung, liver, kidney and other serious diseases;
3. Patients do not cooperate to complete the clinical trial process;
4. Other cases considered unsuitable for inclusion.

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** fzhang@njmu.edu.cn

**Name:** Faming Zhang, PhD

**Phone:** 02558509670

**Role:** CONTACT

**Contact 2:**

**Email:** cuibota@njmu.edu.cn

**Name:** Bota Cui

**Phone:** 02558509883

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Nanjing

**Contacts:**

***Contact 1:***

- **Email:** fzhang@njmu.edu.cn

- **Name:** Faming Zhang, PhD

- **Phone:** 086-025-58509883

- **Role:** CONTACT

**Country:** China

**Facility:** Department of Microbiota Medicine & Medical Centre for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University

**State:** Jiangsu

**Status:** RECRUITING

#### Overall Officials

**Official 1:**

**Affiliation:** The Second Hospital of Nanjing Medical University

**Name:** Faming Zhang, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Wang W, Lu G, Wu X, Wen Q, Zhang F. Colonic Transendoscopic Enteral Tubing Is a New Pathway to Microbial Therapy, Colonic Drainage, and Host-Microbiota Interaction Research. J Clin Med. 2023 Jan 18;12(3):780. doi: 10.3390/jcm12030780.

**PMID:** 36769429

**Citation:** Zhang X, Zhang L, Chan JCP, Wang X, Zhao C, Xu Y, Xiong W, Chung WC, Liang F, Wang X, Miao J, Bian Z. Chinese herbal medicines in the treatment of ulcerative colitis: a review. Chin Med. 2022 Apr 4;17(1):43. doi: 10.1186/s13020-022-00591-x.

**PMID:** 35379276

**Citation:** Gou H, Su H, Liu D, Wong CC, Shang H, Fang Y, Zeng X, Chen H, Li Y, Huang Z, Fan M, Wei C, Wang X, Zhang X, Li X, Yu J. Traditional Medicine Pien Tze Huang Suppresses Colorectal Tumorigenesis Through Restoring Gut Microbiota and Metabolites. Gastroenterology. 2023 Dec;165(6):1404-1419. doi: 10.1053/j.gastro.2023.08.052. Epub 2023 Sep 12.

**PMID:** 37704113

**Citation:** Wei P, He Q, Liu T, Zhang J, Shi K, Zhang J, Liu S. Baitouweng decoction alleviates dextran sulfate sodium-induced ulcerative colitis by suppressing leucine-related mTORC1 signaling and reducing oxidative stress. J Ethnopharmacol. 2023 Mar 25;304:116095. doi: 10.1016/j.jep.2022.116095. Epub 2022 Dec 26.

**PMID:** 36581160

**Citation:** Gu X, Miao Z, Wang Y, Yang Y, Yang T, Xu Y. New Baitouweng decoction combined with fecal microbiota transplantation alleviates DSS-induced colitis in rats by regulating gut microbiota metabolic homeostasis and the STAT3/NF-kappaB signaling pathway. BMC Complement Med Ther. 2022 Nov 24;22(1):307. doi: 10.1186/s12906-022-03766-z.

**PMID:** 36424592

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004194

- Term: Disease

- ID: D000010335

- Term: Pathologic Processes

- 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: 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: M16355

- Name: Syndrome

- Relevance: HIGH

- As Found: Syndrome

- 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: D000013577

- Term: Syndrome

- ID: D000014456

- Term: Ulcer

### Intervention Browse Module - Browse Branches

- Abbrev: HB

- Name: Herbal and Botanical

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: T120

- Name: Cola

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
