DistensionEarly Phase 1NCT04768010
Misoprostol for Bloating and Distension
A Early Phase 1 study testing Misoprostol in people with Distension and Gas Bloat Syndrome, run by Montefiore Medical Center.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Distension, Gas Bloat Syndrome, Constipation
- What is being tested?
- Misoprostol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Aug 2023to 18 Sep 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- hemodialysis
- active infection
- Evidence of bowel obstruction
- Evidence of moderate or large ascites
- history of bowel surgery, uncontrolled thyroid disorders, inflammatory bowel disease
- pregnancy
Show all 10Show fewer
- 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
About this study
Official title: Misoprostol for the Management of Bloating and Gaseous Distension in Patients With Cirrhosis: an Open Label Trial
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.
Read the 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:
- 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
- Radiologic quantitation of intestinal gaseous distension as assessed by volumetric measurement of ultra-low radiation abdominal CT scan
- 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.
- Conditions
- Distension, Gas Bloat Syndrome, Constipation
- Being tested
- Misoprostol
- Medical subject headings
- Dilatation, Pathologic, Gas bloat syndrome, Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MisoprostolDrug
Also called Cytotec (brand name)
Participants will started by receiving 100 micrograms of oral misoprostol twice daily. If adverse effects are not noted dose can be titrated up to 200 micrograms of misoprostol twice daily. Participants will receive a total of five doses.
| Study group | Role | What they receive |
|---|---|---|
| Misoprostol | Experimental | Participants will receive 100-200 micrograms of oral misoprostol twice daily. Receives: Drug: Misoprostol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) Questionnaire Score
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.
Measured: Baseline, Day 2, and Day 3
Change in Patient Assessment of Constipation Symptoms (PAC-SYM) Questionnaire Score
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.
Measured: Baseline, Day 1, Day 2, and Day 3
Secondary outcomes (5)
Change in intestinal gas volume from baseline to post-intervention
Measured by low dose abdominal CT
Measured: Baseline and Day 3
Change in stool burden from baseline to post-intervention
Scored using abdominal X-ray
Measured: Baseline and Day 3
Change in Abdominal Girth
Abdominal girth will be measured in centimeters using a tape measure.
Measured: Baseline, Day 1, Day 2, and Day 3
Change in Psychometric Hepatic Encephalopathy Score (PHES)
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.
Measured: Baseline, Day 2, and Day 3
Change in Abdominal Pain
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).
Measured: Baseline, Day 2, and Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2021
- Study startAug 2023 (estimated)
- Primary completion18 Sep 2023
- Study completion18 Sep 2023
Why it stopped: After significant delays study was never initiated. No participants enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DistensionStudies of the same condition, open and under way.
- More trials run by Montefiore Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montefiore Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Samuel Sigal, MD, Principal investigator, Montefiore Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04768010
- Sponsor's protocol ID
- 2021-12715
- Status last verified
- Sep 2023
- First submitted
- 19 Feb 2021
- Last updated
- 28 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Misoprostol for the Management of Bloating and Gaseous Distension in Patients With Cirrhosis: an Open Label Trial
- ClinicalTrials.gov ID
- NCT04768010
- Acronym / sponsor ID
- 2021-12715
- Conditions
- Distension, Gas Bloat Syndrome, Constipation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: After significant delays study was never initiated. No participants enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Montefiore Medical CenterUniversity, hospital or other
- Study start
- Aug 2023 (estimated)
- Primary completion
- 18 Sep 2023 (actual)
- Study completion
- 18 Sep 2023 (actual)
- First posted
- 24 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
- Radiologic quantitation of intestinal gaseous distension as assessed by volumetric measurement of ultra-low radiation abdominal CT scan
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Misoprostol | Experimental | Drug: MisoprostolParticipants will receive 100-200 micrograms of oral misoprostol twice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (10 listed)
- hemodialysis
- active infection
- Evidence of bowel obstruction
- Evidence of moderate or large ascites
- history of bowel surgery, uncontrolled thyroid disorders, inflammatory bowel disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MisoprostolAlso: Cytotec (brand name)Participants will started by receiving 100 micrograms of oral misoprostol twice daily. If adverse effects are not noted dose can be titrated up to 200 micrograms of misoprostol twice daily. Participants will receive a total of five doses. | Drug | Misoprostol |
Primary outcome
Change in Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) Questionnaire Score
Time frame: Baseline, Day 2, and Day 3
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.
Change in Patient Assessment of Constipation Symptoms (PAC-SYM) Questionnaire Score
Time frame: Baseline, Day 1, Day 2, and Day 3
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.
5 secondary outcomes
Change in intestinal gas volume from baseline to post-intervention
Time frame: Baseline and Day 3
Change in stool burden from baseline to post-intervention
Time frame: Baseline and Day 3
Change in Abdominal Girth
Time frame: Baseline, Day 1, Day 2, and Day 3
Change in Psychometric Hepatic Encephalopathy Score (PHES)
Time frame: Baseline, Day 2, and Day 3
Change in Abdominal Pain
Time frame: Baseline, Day 2, and Day 3
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samuel Sigal, MD principal investigator
Montefiore Medical Center
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Misoprostol in people with Distension and Gas Bloat Syndrome, run by Montefiore Medical Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) Questionnaire Score (time frame: Baseline, Day 2, and Day 3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.