Clinical trial NCT04768010: Misoprostol for Bloating and Distension
Official title: Misoprostol for the Management of Bloating and Gaseous Distension in Patients With Cirrhosis: an Open Label Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Distension
Gas Bloat Syndrome
Constipation
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2021-02-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) Questionnaire Score
timeFrame: Baseline, Day 2, and Day 3
measure: Change in Patient Assessment of Constipation Symptoms (PAC-SYM) Questionnaire Score
timeFrame: Baseline, Day 1, Day 2, and Day 3
Secondary outcomes:
measure: Change in intestinal gas volume from baseline to post-intervention
timeFrame: Baseline and Day 3
measure: Change in stool burden from baseline to post-intervention
timeFrame: Baseline and Day 3
measure: Change in Abdominal Girth
timeFrame: Baseline, Day 1, Day 2, and Day 3
measure: Change in Psychometric Hepatic Encephalopathy Score (PHES)
timeFrame: Baseline, Day 2, and Day 3
measure: Change in Abdominal Pain
timeFrame: Baseline, Day 2, and Day 3
Other outcomes:
Locations:
Study officials:
affiliation: Montefiore Medical Center
name: Samuel Sigal, MD
role: PRINCIPAL_INVESTIGATOR
References: