Cystic Fibrosis and Gut Dysmotility: The Effect of Polyethylene Glycol (PEG) on Intestinal Transit

July 12, 2024 updated by: Dhiren Patel, MD, St. Louis University
The investigators will recruit 15 patients with cystic fibrosis 18 years of age and older who present with constipation. The investigators will assess baseline motility symptoms with a survey. Patients will then ingest a SmartPill (trademark) to obtain baseline motility within the GI lumen. All patients will undergo intervention with taking polyethylene glycol (PEG) or Miralax (brand name) 17 grams once daily. After two weeks of therapy, the patient will repeat the motility survey and again ingest a smart pill to assess the change in motility symptoms while on therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background:

Cystic Fibrosis (CF) is an autosomal recessive disorder involving mutation of the cystic transmembrane conductance regulator (CFTR) protein. The consequences of this genetic mutation leads to dysregulated epithelial fluid transportation. Abnormalities of the CFTR protein have multisystem motility complications - it affects primarily the lungs, pancreas, vas deferens, and the gastrointestinal (GI) tract. Cystic Fibrosis causes multiple issues in the GI tract. The CFTR protein is expressed throughout the GI tract at the apical enterocyte membrane. Per recent studies, it has the highest concentration in the duodenum and decreases as the small bowel terminates into the large intestine. Patients often experience symptoms secondary to dysmotility from abnormal salt and water regulation into the gastrointestinal lumen. Cystic Fibrosis patients are at risk for small intestinal bacterial overgrowth (SIBO), intestinal dysbiosis, inflammation, distal intestinal obstruction syndrome (DIOS), constipation, and postprandial delayed gastric emptying.

Multiple studies have been done to evaluate gastrointestinal motility in the CF patients. One study reviewed gastric muscle rhythms in CF patients via pre and post-prandial electrogastrography (EGG) and found postprandial bradygastria. Patients had symptom improvement with initiation of cisapride however this drug is not FDA approved in different continents. Another study researched GI transit times via the magnet-based motility tracking system and found increased transit in the upper small intestine compared to control populations. Overall, CF patients were found to have delayed small intestine transit time with the magnetic pill reaching the cecum in only 2 of 10 CF patients in a 7 hour period compared to 14 of 16 control patients. Hydrogen Breath tests have diagnosed SIBO in CF patients however overall delay in intestinal transit affect interpretation of results. Empiric treatment with antibiotics or laxatives is recommended with some improvement in patient symptoms. Mouse studies have shown that use of Miralax (brand name) or polyethylene glycol (PEG) laxative decreased bacterial overgrowth in 90% of Cystic Fibrosis mice. Further studies showed that daily PEG use decreases positive breath tests in a small study of CF patients. While there have been multiple studies showing symptomatic improvement of SIBO and DIOS with PEG and/or other laxative agents, none have measured whether or not these medications improve intestinal transit time. The aim of this research project is to evaluate total intraluminal transit time in CF patients and the effects of PEG on transit time and patient symptoms.

Study Description:

This is a prospective cohort study. This is an investigator initiated study. Once enrolled, patients will spend a total of 4 weeks in the study. All participants will receive the intervention. There will be no randomization in this study.

Information pulled from the patient's medical record includes the patient's name, medical record number, date of birth, cystic fibrosis genotype, medication list, and medical history.

Study Procedures:

  1. Initial recruiting visit: Informed consent to participate in the research study will be obtained.The patient will need to have a 2 week washout period where all non-essential medications that alter gut motility are temporarily stopped. The medications withheld will be at the discretion of the physician.This list will be provided to the patient. The patients on pancreatic enzyme replacement must remain on this as to not affect study outcomes.

  2. Second visit: The patient will complete Rome IV Diagnostic Questionnaire (R4DQ) for Functional Gastrointestinal Disorders in Adults (FGIDs). This Questionnaire is considered a research procedure. Once procedural informed consent is obtained, the patient will be fitted for the recorder and ingest the SmartPill. The patient will return the receiver up to seven days after the capsule was ingested.The SmartPill is considered a research procedure. If the SmartPill is not excreted after day 7, the patient will obtain an outpatient abdominal X-ray to determine if the SmartPill device is retained in the intestines. A pregnancy test will be performed prior to any potential radiation exposure for female patients of child-bearing ages, 13-50 years old. The X-ray, if completed, is considered a research procedure.

    **If there is concern the SmartPill may be retained in the intestine, the patient may be asked to take a Patency agile capsule. This will require the patient to obtain a abdominal X-ray 24 hours after ingestion as an outpatient to localize the capsule's location. This is considered standard of care.

  3. Study period (two weeks): After 7 days, the patient will begin intervention with polyethylene glycol (PEG) 17 g therapy for total of 2 weeks. If persistent symptoms (no bowel movements in > 24 hours, abdominal pain, straining, bloating), then the patient can increase to 17 g twice daily. The patient will call the office after 1 week to determine if step up to twice daily therapy is warranted.

    The patients will receive a log to record time of PEG ingestion, if PEG was taken with meals, a log of other medications taken during the intervention timeline, and recording symptoms of constipation. Patients will be advised to avoid non-essential drugs that can alter gut motility (see attached list found on the patient log) during the treatment period. The study drug is considered standard of care procedure.

  4. Third visit: Two weeks following initiation of therapy, the patient will repeat the Rome IV Diagnostic Questionnaire for Adult FGIDs (R4DQ) and ingest the second SmartPill to assess for change in gut motility. Procedural informed consent will be obtained prior the questionnaire and ingestion of the SmartPill. This Questionnaire and SmartPill device is considered a research procedure. The patient will return the receiver up to seven days after the capsule was ingested.The SmartPill is considered a research procedure. If the SmartPill is not excreted after day 7, the patient will obtain an outpatient abdominal XRay to determine if the SmartPill device is retained in the intestines. A pregnancy test will be performed prior to any potential radiation exposure for female patients of child-bearing ages, 13-50 years old.The X Ray, if completed, is considered a research procedure.

    **If there is concern the SmartPill may be retained in the intestine, the patient may be asked to take a Patency agile capsule. This will require the patient to obtain a abdominal X Ray 24 hours after ingestion as an outpatient to localize the capsule's location. This is considered standard of care.

  5. Fourth visit: The patient will return the recorder equipment for analysis and will complete a post study questionnaire and undergo review of their therapy log detailing how the medication was taken. This Questionnaire is considered a research procedure.

The subject participation in the study ends at this point.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63104
        • SSM Health Cardinal Glennon Children's Hosptial
      • Saint Louis, Missouri, United States, 63104
        • SSM Health Saint Louis University Hosptial

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • previously diagnosed with CF confirmed with genetic mutations consistent with CF
  • greater than 18 years old who chose to participate in the research study
  • have symptoms of constipation (constipation will be defined as stool frequency less than three times per week, Bristol stool scale form 1-2 in >25% of stools, and/or the sensation of incomplete evacuation, manual maneuvers to facilitate stools, and the sensation of blockage)

The patients enrolled are allowed to be on CFTR modulating drugs and/or receiving enteral feeding.

Exclusion Criteria:

  • minors (<18 years old)
  • active nicotine use or patients on nicotine replacement
  • history of abdominal surgery (surgeries involving gastrointestinal luminal resection) ie small bowel or colonic resection that increases risk of post-operative strictures or narrowing of the lumen. Surgeries such as Nissen fundoplication, gastrostomy tube placement, gynecologic surgeries, appendectomy, and/or cholecystectomy are not excluded from this study.
  • history of lung transplantation or pancreas transplant
  • BMI >40
  • pregnancy (this will be screened via urine pregnancy test)
  • incarcerated persons
  • patients with DIOS (distal intestinal obstructive syndrome)
  • patients with known hypersensitivity to PEG
  • persons unable to remain off the contraindicated medications.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention with polyethylene glycol & SmartPill
Patients will ingest a Smart pill to obtain baseline motility within the GI lumen. All patients will undergo intervention with taking polyethylene glycol (PEG) or Miralax (brand name) 17 grams once daily. After two weeks of therapy, the patient will repeat the motility survey and again ingest a smart pill to assess the change in motility symptoms while on therapy.
Drug: Polyethylene Glycol 3350
All patients will undergo intervention with taking polyethylene glycol (PEG) or Miralax (brand name) 17 grams once daily for total of 2 weeks.
Device: SmartPill Motility System & PillCam Patency Capsule
Patients will ingest a Smart pill to obtain baseline motility within the GI lumen. After two weeks of therapy, the patient will repeat the motility survey and again ingest a smart pill to assess the change in motility symptoms while on therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change is Being Assessed: Total Intestinal Transit Time at Baseline and Two Weeks Following Initiation of Therapy
Time Frame: Change is being assessed: total intestinal transit time (measured in hours) at baseline and two weeks following initiation of therapy with PEG
Total intestinal transit time will be measured from the time of ingestion to time of expulsion of smartpill. Unit of measurement will be hours.
Change is being assessed: total intestinal transit time (measured in hours) at baseline and two weeks following initiation of therapy with PEG
Number of Participants With IBS at Baseline and 2 Weeks Post Baseline
Time Frame: Baseline and 2 weeks

Subjective assessment for abdominal symptoms with ROME questionnaire. Note that the outcome of these questionnaire is IBS present or absent.Rome 4 is a self-report integrated questionnaire in adults (R4DQ), including alarm symptoms or red flags.

ROME 4 IBS present if:

Recurrent abdominal pain on average at least 1 day/week in the last 3 months, associated with two or more of the following criteria:

Related to defecation Associated with a change in frequency of stool Associated with a change in form (appearance) of stool

Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis.

Rome 4 IBS absent if not fulfilled as above.
Baseline and 2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Louis University

Investigators

  • Principal Investigator: Dhiren Patel, MD, St. Louis University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 12, 2019

Primary Completion (Actual)

June 6, 2023

Study Completion (Actual)

June 6, 2023

Study Registration Dates

First Submitted

December 18, 2019

First Submitted That Met QC Criteria

December 20, 2019

First Posted (Actual)

December 24, 2019

Study Record Updates

Last Update Posted (Actual)

August 9, 2024

Last Update Submitted That Met QC Criteria

July 12, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 30114

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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