A Study of Herbal Supplements in Cancer Survivors With Constipation

Herbal Formula Ma-Zi-Ren-Wan (MZRW) on Bowel Movement Function and Gut Microbiome Among Cancer Survivors With Constipation: A Double-blinded Randomized Controlled Trial (RELIEVE)

The purpose of this study is to find out whether MZRW is an effective treatment for constipation in cancer survivors. The researchers will compare MZRW with placebo, a pill that looks like MZRW and is given in the same way, but contains no medication. The researchers will also study the effect MZRW has on the gut microbiome. The gut microbiome is a diverse community of microorganisms living in the digestive system, essential for digestion and immune function.

Inclusion Criteria:

• Age 18 years or greater;

• A diagnosis of cancer with no restrictions placed on type of cancer or stage;

• Completed surgery, chemotherapy, immunotherapy, and/or radiotherapy, or an investigational therapy at least one month prior to study initiation. Patients on stable doses of hormone therapy or targeted therapies will not be excluded;

• Karnofsky functional score of ≥ 60;

• Cancer survivors who have met the Rome IV criteria (Table 3) of the symptoms of functional constipation which must include two or more of the following:

  • Straining more than 25% of defecations.
  • Lumpy or hard stools (7-point Bristol stool scale 1 or 2) more than 25% of defecations.
  • Sensation of incomplete evacuation more than one-fourth (25%) of defecations.
  • Sensation of anorectal obstruction/blockage more than one-fourth (25%) of defecations.
  • Manual maneuvers to facilitate more than one-fourth (25%) of defecations.
  • Fewer than three spontaneous bowel movements per week.
  • Loose stools are rarely present without the use of laxatives.
  • Insufficient criteria for irritable bowel syndrome.

• Patient should be able to understand and complete all study assessments on their own

• Patient should be able to understand and provide signed informed consent in English.

Table 3. Rome IV criteria for functional constipation FUNCTIONAL CONSTIPATION Diagnostic criteria*

1. Must include two or more of the following:**
2. Straining during more than ¼ (25%) of defecations
3. Lumpy or hard stools (Bristol Stool Form Scale 1-2) more than ¼ (25%) of defecations
4. Sensation of incomplete evacuation more than ¼ (25%) of defecations
5. Sensation of anorectal obstruction/blockage more than ¼ (25%) of defecations
6. Fewer than three SBM per week
7. Manual maneuvers to facilitate more than ¼ (25%) of defecations (e.g., digital evacuation, support of the pelvic floor)

9. Loose stools are rarely present without the use of laxatives 9. Insufficient criteria for irritable bowel syndrome Note *Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis

Exclusion Criteria:

• Patients who have allergic history to herbs or Chinese medicine;
• Clinically significant abnormal liver (2 times the ULN for ALT or AST) and kidney disfunction(eGFR below 59 mL/min/1.73m² ) from recent laboratory test recorded in the medical record (within 2 month);
• Patients who have any signs of bowel obstruction, or have high risk of bowel obstruction assessed by their treating physician, including factors such as tumor invasion into abdominal organs, recent abdominal surgery, and prior abdominal radiation therapy;
• Patients who are prescribed opioid antagonists including methylnaltrexone, naloxegol and naldemedine for opioid induced constipation and required not to stop the medication;
• Women who are pregnant, lactating, or not practicing proper contraception by patient report.Patient's should follow proper contraception guidelines for at least 30 days following last dose of the study drug.