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.
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.
Brief Title
Misoprostol for Bloating and Distension
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Distension
Gas Bloat Syndrome
Constipation
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04768010
Org Class
Other
Org Full Name
Montefiore Medical Center
Org Study Id
2021-12715
Overall Status
Withdrawn
Phases
Early Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Misoprostol for the Management of Bloating and Gaseous Distension in Patients With Cirrhosis: an Open Label Trial
Primary Outcomes
Outcome Description
The PAGI-SYM is a validated 20 item self-report questionnaire divided in to six domains: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain. Scores for each question range from 0 (none absent) to 5 (very severe). This questionnaire obtains subscale scores derived from the average scores across these six domains. The original questionnaires asks "How severe have each of these following symptoms been in the past two weeks?" For the purpose of this study, we have obtained manufacturer approval to modify the questionnaire to ask about symptoms severity in the past day.
Outcome Measure
Change in Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) Questionnaire Score
Outcome Time Frame
Baseline, Day 2, and Day 3
Outcome Description
The PAC-SYM is a validated 12 item self-report questionnaire divided into abdominal, rectal, and stool domains. The questionnaire has 4 items for abdominal symptoms, 3 items for rectal symptoms, and 5 items for stool symptoms. Scores range from 0 (none or absent) to 4 (very severe). The total score is the mean of the individual item scores.The original questionnaires asks "How severe have each of these following symptoms been in the past two weeks?" For the purpose of this study, we have obtained manufacturer approval to modify the questionnaire to ask about symptoms severity in the past day.
Outcome Measure
Change in Patient Assessment of Constipation Symptoms (PAC-SYM) Questionnaire Score
Outcome Time Frame
Baseline, Day 1, Day 2, and Day 3
Secondary Outcomes
Outcome Description
Measured by low dose abdominal CT
Outcome Time Frame
Baseline and Day 3
Outcome Measure
Change in intestinal gas volume from baseline to post-intervention
Outcome Description
Scored using abdominal X-ray
Outcome Time Frame
Baseline and Day 3
Outcome Measure
Change in stool burden from baseline to post-intervention
Outcome Description
Abdominal girth will be measured in centimeters using a tape measure.
Outcome Time Frame
Baseline, Day 1, Day 2, and Day 3
Outcome Measure
Change in Abdominal Girth
Outcome Description
The PHES is a series of five neuropsychological tests used in the diagnosis of minimal hepatic encephalopathy. The tests used in this score include the digit-symbol test, number connection tests A and B, the serial dotting test, and the line-drawing test. The final score for the PHES is derived from the sum of the scores of these individual tests. To determine individual test scores, the difference between the predicted and observed results for each test are divided by the corresponding standard deviation (SD) for the reference population to obtain the deviation from 'normal' as a multiple of the SD. Final scores range from -15 to +5. Lower scores are found in patients with encephalopathy, with a score \<-4 SD being considered to represent the presence of minimal hepatic encephalopathy.
Outcome Time Frame
Baseline, Day 2, and Day 3
Outcome Measure
Change in Psychometric Hepatic Encephalopathy Score (PHES)
Outcome Description
The severity of abdominal pain will de determined from the individual Likert score derived from the Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM). The Likert scale ranges from Scores for each question range from 0 (none absent) to 5 (very severe).
Outcome Time Frame
Baseline, Day 2, and Day 3
Outcome Measure
Change in Abdominal Pain
Start Date
Start Date Type
Estimated
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Samuel Sigal
Investigator Email
ssigal@montefiore.org
Investigator Phone
718-920-6240
Categories Mesh Debug
Digestive System --- DILATATION, PATHOLOGIC
Digestive System --- CONSTIPATION
Digestive System --- SIGNS AND SYMPTOMS, DIGESTIVE
MeSH Terms
DILATATION, PATHOLOGIC
GAS BLOAT SYNDROME
CONSTIPATION
PATHOLOGICAL CONDITIONS, ANATOMICAL
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
SIGNS AND SYMPTOMS, DIGESTIVE
SIGNS AND SYMPTOMS
MISOPROSTOL
PROSTAGLANDINS E, SYNTHETIC
PROSTAGLANDINS, SYNTHETIC
PROSTAGLANDINS
EICOSANOIDS
FATTY ACIDS, UNSATURATED
FATTY ACIDS
LIPIDS
AUTACOIDS
INFLAMMATION MEDIATORS
BIOLOGICAL FACTORS