Clinical trial NCT02798458: Evaluation of the Gastrointestinal Manifestation of Fabry's Disease
Official title: Evaluation of the Gastrointestinal Manifestation of Fabry's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fabry's Disease
Keywords: Fabry's Disease
Fabry
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2016-06-14
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Patients will undergo a SmartPill test to gain additional understanding of Fabry disease manifestation via motility abnormalities in order to improve symptom targeted therapy. An additional Endoscopic mucosal resection may be performed on further qualifying patients. Tissue analysis from this biopsy will include evaluation of abnormalities of cellular structure and morphology with correlation with gastrointestinal complaints for each patient and comparison against age matched non-Fabry patient tissue. The hypothesis is that patients with fabry disease will have abnormal motility which will correlate with the patients symptoms and quality of life as noted on the questionnaires.

Detailed description: Background: Gastrointestinal manifestations such as abdominal pain, diarrhea and nausea are prominent and, although typically non life-threatening, can frequently cause significant morbidity and burden in a patient with Fabry disease. Additional in depth understanding of gastrointestinal symptoms pathophysiology in Fabry disease is acutely needed in order to develop more specific evaluation of the symptoms and advance the treatment of these patients.

Hypothesis: Patients with gastrointestinal (GI) symptoms will have delayed motility on the SmartPill study, abnormal histologic findings on mucosal resection and symptoms that correlate with abnormal histologic and SmartPill findings. By gaining additional insight into the characterization of symptoms and the relationship to dysmotility, we anticipate improved and more focused adjunct therapies for the patients.

Methods: This study will consist of a screening visit, a SmartPill testing procedure visit, and a follow up visit for all subjects enrolled in the study. Fifteen of these patients, who clinically warranted sigmoidoscopy, will be asked to also complete an endoscopic mucosal resection (EMR) visit in addition to the other aspects of the study. Thus, each subject will report to the study site for at least 3 visits and up to 4 visits.

Eligibility criteria: Inclusion Criteria:

* Adults ages 18-70 years who have diagnosed Fabry disease either by enzyme testing in males or by enzyme and/or genetically confirmed mutation in females.
* Adults with Fabry disease having any gastrointestinal complaints within the past year.
* Endoscopic Mucosal Resection ONLY - Symptomatic subjects necessitating a sigmoidoscopy who are enzyme replacement therapy (ERT) naive OR less than 6 months of treatment.

Exclusion Criteria:

1. Fabry disease with other concomitant gastrointestinal diagnosis (Example:

   Inflammatory Bowel Disease, Celiac Disease)
2. Pregnancy
3. Endoscopic mucosal resection exclusions:

   1. Any contraindication to conscious sedation,
   2. Contraindication to endoscopy,
   3. Untreated or unmanageable coagulopathy,
   4. Thrombocytopenia (\<50).
   5. Patient on ERT for more than 6 months.
4. Exclusions for SmartPill:

   1. Previous history of bezoars.
   2. Prior GI surgery except for cholecystectomy, appendectomy, or Nissen fundoplication.
   3. Any abdominal surgery within the past 3 months
   4. History of diverticulitis, diverticular stricture, and other intestinal strictures
   5. Tobacco use within eight hours prior to capsule ingestion and during the initial 8-hour recording on Day 0 or the Ingestion visit.
   6. Alcohol use within eight hours prior to capsule ingestion and throughout the entire monitoring period (5 days).
   7. BMI \> 38
   8. Allergies to components of the SmartBar
   9. Use of medical devices such as pacemakers, infusion pumps, or insulin pumps.
   10. Uncontrolled diabetes with a hemoglobin A1C greater than 10.

Primary outcomes:
measure: Gastric Emptying Transit Time Measured Via SmartPill Study
timeFrame: Up to 5 hours
measure: Small Bowel Transit Time Measured Via SmartPill Study
timeFrame: Up to 6 hours
measure: Colonic Transit Time Measured Via SmartPill Study
timeFrame: Up to 67 hours
Secondary outcomes:
measure: Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires
timeFrame: Up to 4 weeks
measure: Age of Symptom Start
timeFrame: Up to 4 weeks
measure: Delayed Gastric Emptying Measured Via SmartPill Study
timeFrame: Up to 5 hours
measure: Delayed Small Bowel Transit Measured Via SmartPill Study
timeFrame: Up to 6 hours
measure: Delayed Colonic Transit Measured Via SmartPill Study
timeFrame: Up to 67 hours
measure: Symptom Severity Index
timeFrame: At 67 hours, data reported over the last 4 weeks
measure: Symptom Frequency Assessment (SFA)
timeFrame: At 67 hours, data reported over the last 7 days
measure: Hamilton Anxiety Rating Scale (HAM-A)
timeFrame: At 4 weeks
measure: Beck's Depression Inventory (BDI)
timeFrame: At 4 weeks
measure: Work Productivity and Activity Impairment (WPAI)
timeFrame: At 7 days
measure: IBS Quality of Life (IBS QoL) and Sub-scores
timeFrame: At 4 weeks
measure: Bristol Stool Scale
timeFrame: At 7 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Braden Kuo, MD
role: PRINCIPAL_INVESTIGATOR
References: