Misoprostol for Bloating and Distension

Montefiore Medicine Academic Health System

Status and phase: Withdrawn; Early Phase 1

Conditions: Gas Bloat Syndrome; Constipation; Distension

Treatments: Drug: Misoprostol

Study type: Interventional

Funder types: Other

Identifiers

NCT04768010

2021-12715

Details and patient eligibility

About

Symptoms of bloating, abdominal distension, and constipation are common in patients with cirrhosis. These symptoms may be explained by disease-associated effects in gastrointestinal physiology, as well as medication side-effects. The presence of these symptoms affect quality of life, as well as risk for encephalopathy. Misoprostol is a synthetic prostaglandin approved for the treatment prevention of NSAID-induced gastric ulcers. The drug also causes smooth muscle contraction in the gastrointestinal tract has been shown to improve colonic motility.

This study aims to assess the efficacy of misoprostol for treating bloating, distension, and constipation in patients with cirrhosis. Study participants will receive misoprostol for a duration of three days. Participants will complete pre-intervention and post-intervention symptom questionnaires and low dose abdominal computed tomography (CT) scan. These measures will be used to assess subjective symptom scores and objective measurement of intestinal gas and colonic stool. Post-intervention measures will be compared to pre-intervention measures to assess improvement of symptoms.

Full description

Specific Aims of Study:

To determine whether misoprostol is beneficial in patients with cirrhosis with bloating secondary to stool and gaseous distension, patient with marked symptoms that are refractory to standard of care will receive open label Misoprostol (100mcg twice daily and increased to 200mcg twice daily based on response) before and after 2 days of treatment with the following assessments:

1. Characterization of bloating and abdominal discomfort symptoms as assessed by the Patient Assessment of Constipation (PAC-SYM) and Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) Questionnaires composite scores and subscale scores before
2. Radiologic quantitation of intestinal gaseous distension as assessed by volumetric measurement of ultra-low radiation abdominal CT scan
3. Impact on severity of hepatic encephalopathy scores as assessed by West Haven criteria grading and Psychometric Hepatic Encephalopathy Score (PHES)

This study is a prospective, open-label trial comparing the efficacy of misoprostol in the management of bloating and gaseous distension in patients with cirrhosis.

The duration of the study will be over 3 days for each enrolled patient and will include an initial screening encounter prior to day 1 of the study period. During the screening encounter, participants' will receive a complete history and physical including review of treatment with standard of care treatments such as polyethylene glycol, bisacodyl, docusate, senna, and simethicone. If symptoms are not relieved by the use of these standard of care treatments participants will be fully screened, provided informed consent, enrolled in the trial.

Participants will be administered the PAC-SYM, PAGI-SYM questionnaires in addition to determination of West Haven Criteria Grade and PHES. These baseline demographics will be collected and used as reference for comparison of post-intervention questionnaire results. Baseline abdominal girth will also be documented. Afterwards, participants will receive a baseline low-dose abdominal CT for the volumetric assessment of intestinal gas. Abdominal X-ray available from CT data will be used for scoring of colonic stool burden.

Participants will be started on the study medication on day 1. On day 1, participants will receive an initial dose of 100 micrograms of misoprostol administered orally. The patient will be monitored for adverse effects and, if none observed, will continue 100 microgram dose twice daily with increase to 200mcg on day 2 if symptoms not improved. All primary outcomes will be assessed daily between morning and evening doses.

On the morning of day 3, participants will receive one dose of study drug at dose received on day 2. After administration of the drug, participants will repeat ultra-low dose abdominal CT and complete a final assessment with the PAC-SYM, PAGI-SYM, PHES and West Haven Grading.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age > 18 years old
• Participants who voluntarily sign and date an informed consent
• Participants who are willing to adhere to the procedures in this protocol
• Have biopsy or strong clinical evidence for the presence of cirrhosis
• Report any of the following symptoms: abdominal bloating, distension, and/or constipation (<3 bowel movements per week)
• Have failed management with standard-of-care therapies used at Montefiore Medical Center
• Have received a standard-of-care abdominal x-ray revealing gaseous distension or fecal loading

Exclusion criteria

• hemodialysis
• active infection
• Evidence of bowel obstruction
• Evidence of moderate or large ascites
• history of bowel surgery, uncontrolled thyroid disorders, inflammatory bowel disease
• pregnancy
• intubation during current hospitalization
• inability to provide informed consent.
• History of allergic reaction to prostaglandins
• Patients on narcotic medications besides a stable dose of methadone

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

Misoprostol

Experimental group

Description:

Participants will receive 100-200 micrograms of oral misoprostol twice daily.

Treatment:

Drug: Misoprostol