Evaluation of the Gastrointestinal Manifestation of Fabry's Disease

• ClinicalTrials.gov Identifier: NCT02798458
• Recruitment Status: Recruiting
• First Posted: June 14, 2016
• Last Update Posted: February 24, 2021
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Branden Kuo, Massachusetts General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fabry's Disease	Device: Smartpill; Procedure: Endoscopic Mucosal Resection	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Evaluation of the Gastrointestinal Manifestation of Fabry's Disease
• Study Start Date: May 2016
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: SmartPill Test; All subjects will be asked to complete a SmartPill test. The SmartPill capsule is pill-shaped and about an inch long and ½ inch wide, or about the size of a vitamin pill. The receiver unit is about the size of a paperback book. The receiver gets signals from the capsule and stores the signals on a computer chip. The capsule detects the level of acidity, temperature, and pressures in your stomach and intestines and sends the information by radio wave signals to the receiver.	Device: Smartpill; The SmartPill Test is approved by the U.S. Food and Drug Administration (FDA) to measure transit time in the GI tract. This procedure uses the SmartPill capsule, a receiver, and computer software.
Experimental: Endoscopic Mucosal Resection; An additional small group of subjects will also be asked to complete a Sigmoidoscopy (an exam used to evaluate the lower part of the large intestine) during which an Endoscopic Mucosal Resection (removal of a small amount of tissue from the outermost layer of gut wall) will be completed. In the Endoscopy Mucosal Resection (EMR) procedure we will use an instrument called an endoscope (a lighted, flexible tube) to take a tissue sample from the rectum. This is the same type of instrument used in a routine colonoscopy	Device: Smartpill; The SmartPill Test is approved by the U.S. Food and Drug Administration (FDA) to measure transit time in the GI tract. This procedure uses the SmartPill capsule, a receiver, and computer software.; Procedure: Endoscopic Mucosal Resection; a Sigmoidoscopy is an exam used to evaluate the lower part of the large intestine) during which an Endoscopic Mucosal Resection (removal of a small amount of tissue from the outermost layer of gut wall) will be completed.

Outcome Measures

Primary Outcome Measures :

1. Gastrointestinal Transit time measured via SmartPill study [ Time Frame: 2 years ]
   The primary outcome of dysmotility will be the measurement of transit time via a SmartPill study. The transit time will be reported as gastric time, small bowel time and colonic time in additional to total transit time.

Secondary Outcome Measures :

1. Gastrointestinal symptom assessment via questionnaires [ Time Frame: 2 years ]
   Participants will complete several questionnaires during study participation regarding gastrointestinal symptoms (lower and upper GI). These results will be used to determine overall gastrointestinal involvement and will be correlated with transit time and histologic findings
2. Extent of injury and deposition in rectal tissue via histologic assessment [ Time Frame: 2 years ]
   Via deep specimen biopsies the extent of deposits and injury will be assessed. Deposit quantification will be determined based on a scale use previously for analysis in Fabry disease (0 No deposit, +deposit present in a few cells, ++ deposits present in some cells, +++ deposits present in many cells). Additionally, the specimens will be assessed for presence or absence of neuronal swelling, myelination, vascular sclerosis, intimal fibrosis and hypertrophy of the smooth muscles of the arterioles. The results of analysis of all specimens will be compared to healthy aged-matched controls obtained from banked specimens in the pathology department.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Claire Zar-Kessler, MD; 617-726-0196; czarkessler@mgh.harvard.edu

Locations

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Fatima U Rao, BA 617-724-0480 frao@mgh.harvard.edu

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

• Principal Investigator: Braden Kuo, MD; Massachusetts General Hospital

More Information

• Responsible Party: Branden Kuo, Instructor in Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02798458
• Other Study ID Numbers: 2015P000097
• First Posted: June 14, 2016
• Last Update Posted: February 24, 2021
• Last Verified: February 2021

Keywords provided by Branden Kuo, Massachusetts General Hospital:

Fabry's Disease; Fabry

Additional relevant MeSH terms:

Fabry Disease; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders