ND-12 Combined With H-6 for Adult Chronic Inflammatory Diarrhea

A Randomised, Controlled, Double-blind Exploratory Study of ND-12 Combined With H-6 in the Treatment of Adult Chronic Inflammatory Diarrhea

This is a randomized controlled trial to explore the efficacy and safety of ND-12 combined with H-6 for patients with chronic inflammatory diarrhea

At least 36 subjects who meet all the inclusion criteria but do not meet any exclusion criteria will be enrolled in this study. They will be randomly assigned to the mesalazine group , ND-12, and the ND-12/H-6 group. Data of demographic characteristics, intestinal symptoms, medicine treatment usage and clinical outcomes will be collected. After treatment, they will enter the follow-up period for efficacy and safety evaluation.

Inclusion Criteria:

1. Subjects aged 18-75 years (inclusive), of any gender.
2. Meet any one of the following conditions:

1） Previously diagnosed ulcerative colitis, currently in the active phase; 2） Diagnosis of chronic diarrhoea: stool frequency ≥3 times per day or markedly higher than the subject's usual baseline; disease duration >4 weeks; recurrent diarrhoea with an interval of 2-4 weeks between episodes; loose stools (Bristol Stool Form Scale type 5, 6, or 7).

3. Faecal calprotectin >150 μg/g. 4.The subject or their legal representative provides informed consent by voluntarily signing the informed consent form, fully understands the study objectives, maintains effective communication with investigators, and is capable of understanding and complying with all requirements specified in this study protocol.

Exclusion Criteria:

Exclusion criteria related to chronic diarrhoea

1. Presence of any of the following symptoms:

   1. Fever ≥37.5°C;
   2. Moderate-to-severe dehydration requiring intravenous fluid replacement;
   3. Recurrent vomiting.

2. Diarrhoea caused by enteric pathogens (e.g., Clostridioides difficile, Salmonella typhi, etc.).

3. Underlying diseases that may trigger diarrhoea, including hyperthyroidism, gastrointestinal autonomic nervous dysfunction, gastrointestinal malignancy, Crohn's disease, history of colectomy (appendectomy, haemorrhoid surgery and fistula-in-ano surgery excluded), history of small-bowel resection (>20 cm of resected intestinal segment), etc.

   Drug-related exclusion criteria

4. Suspected drug-induced diarrhoea (e.g., long-term use of laxatives, antibiotics, chemotherapeutic agents, etc.) where discontinuation of the offending drug is not feasible.

5. History of allergy to any component of mesalazine capsules, ND-12 capsules or H-6 capsules.

6. Anticipated need for prohibited medications during the study (e.g. antibiotics, antidiarrhoeals, antiemetics, antispasmodics, etc.).

7. Use of any investigational drug within 30 days prior to enrolment into this study.

   Other gastrointestinal exclusion criteria

8. History of gastrectomy or vagotomy.

9. Known malabsorptive disorders include coeliac disease.

10. Known lactose intolerance.

11. Any suspected condition requiring abdominal surgery. Other exclusion criteria

12. Confirmed human immunodeficiency virus (HIV) positive status, known or suspected immunosuppression.

13. Known severe hepatic or renal insufficiency.

14. Past or current history of alcohol abuse and/or known substance abuse (cocaine, heroin, cannabis, etc.).

15. Any psychiatric condition impairing the subject's ability to understand the nature, scope and potential consequences of the study, and/or documented evidence of non-cooperation.

16. Pregnant or lactating women.