Clinical trial NCT04210427
Conditions: Cystic Fibrosis Gastrointestinal Disease
Keywords: Cystic Fibrosis Gut Dysmotility Polyethylene Glycol
Sponsor: St. Louis University
Start date: 2019-12-12; Completion date: 2023-06-06
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Arms: arm 1: 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.
Interventions: intervention 1: Polyethylene Glycol 3350 intervention 2: SmartPill Motility System & PillCam Patency Capsule
Intervention descriptions: intervention 1: All patients will undergo intervention with taking polyethylene glycol (PEG) or Miralax (brand name) 17 grams once daily for total of 2 weeks. intervention 2: 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.

Protocol documents:
Prot_SAP_001.pdf: 
ID: 30114 Cystic Fibrosis and Gut Dysmotility: The Effect of 
Polyethylene Glycol (PEG) on Intestinal Transit 
NCT04210427 
Date: 06/08/2023 
 
Background: 
Cystic Fibrosis (CF) is an autosomal recessive disorder involving mutation of the cystic 
transmembrane conductance regulator (CFTR) protein. The consequence 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 (1). 
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 CF patients. 
Bentur et al studied gastric muscle rhythms in CF patients via pre- and post-prandial 
electrogastrography (EGG) and found postprandial bradygastria (2). Patients had 
symptom improvement with initiation of cisapride however this drug is not FDA approved 
in different continents. Hedsund et al studied GI transit times via the magnet-based 
motility tracking system and found increased transit in the upper small intestine compared 
to control populations (3). 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 mice1. 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 these medications improve intestinal transit time.  


Objective: The main goal 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.  Primary 
outcomes include gastrointestinal transit time and symptom improvement. 
Design and Methods: 
This is a prospective cohort study. This is also an investigator-initiated study. Once 
enrolled, patients will spend 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 Protocol 
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 
so 
as 
to 
not 
affect 
study 
outcomes. 
 
2. Second visit: The patient will complete Rome IV Diagnostic Questionnaire for 
Adult FGIDs (R4DQ); 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. 
 
Statistical Plan: 
The data analyzed includes SmartPill endoscopic studies and Rome IV Diagnostic 
Questionnaire for Adult FGIDs (R4DQ). Statistical analysis will compare the relationship 
of GI transit time pre and post treatment.  
Statistical Analysis 
Final statistical analysis will be completed with a Department of Health Sciences 
statistician. Results are considered statistically significant using a p value of <0.05 alpha 
level. 
 


Due to less-than-optimal numbers of participants, this study was closed after enrolling 
three patients. Therefore, the above statistical methods could not be applied. No data 
analysis was performed due to insufficient data.