Cystic Fibrosis and Gut Dysmotility: The Effect of Polyethylene Glycol (PEG) on Intestinal Transit
Condition: Cystic Fibrosis Gastrointestinal Disease
MeSH terms: Cystic Fibrosis; Gastrointestinal Diseases; Digestive System Diseases; Fibrosis
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

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.
    

Intervention name(s): Polyethylene Glycol 3350; SmartPill Motility System & PillCam Patency Capsule
Intervention type(s): Drug; Device
Intervention description(s): All patients will undergo intervention with taking polyethylene glycol (PEG) or Miralax (brand name) 17 grams once daily for total of 2 weeks.; 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.
Intervention MeSH terms: Polyethylene glycol 3350
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cystic Fibrosis; Gut Dysmotility; Polyethylene Glycol