Evaluation of the Gastrointestinal Manifestation of Fabry's Disease

• ClinicalTrials.gov Identifier: NCT02798458
• Recruitment Status: Completed
• First Posted: June 14, 2016
• Results First Posted: March 27, 2023
• Last Update Posted: March 27, 2023
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Braden 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)
• Actual Enrollment: 48 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
• Actual Primary Completion Date: November 10, 2021
• Actual Study Completion Date: November 2022

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. Gastric Emptying Transit Time Measured Via SmartPill Study [ Time Frame: Up to 5 hours ]
   The primary outcome of dysmotility will be the measurement of gastric emptying transit time via a SmartPill study. Delayed GET are defined as longer than 5 hours.
2. Small Bowel Transit Time Measured Via SmartPill Study [ Time Frame: Up to 6 hours ]
   The primary outcome of dysmotility will be the measurement of small bowel transit time via a SmartPill study. Delayed SBTT are defined as longer than 6 hours.
3. Colonic Transit Time Measured Via SmartPill Study [ Time Frame: Up to 67 hours ]
   The primary outcome of dysmotility will be the measurement of colonic transit time via a SmartPill study. Delayed CTT is defined as longer than 59 hours.

Secondary Outcome Measures :

1. Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires [ Time Frame: Up to 4 weeks ]
   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. Age of Symptom Start [ Time Frame: Up to 4 weeks ]
3. Delayed Gastric Emptying Measured Via SmartPill Study [ Time Frame: Up to 5 hours ]
   The secondary outcome of dysmotility will be the measurement of delayed gastric emptying measured via a SmartPill study. Delayed GET are defined as longer than 5 hours.
4. Delayed Small Bowel Transit Measured Via SmartPill Study [ Time Frame: Up to 6 hours ]
   The secondary outcome of dysmotility will be the measurement of delayed bowel transit time via a SmartPill study. Delayed SBTT are defined as longer than 6 hours.
5. Delayed Colonic Transit Measured Via SmartPill Study [ Time Frame: Up to 67 hours ]
   The secondary outcome of dysmotility will be the measurement of delayed colonic transit time via a SmartPill study. Delayed CTT is defined as longer than 59 hours.
6. Symptom Severity Index [ Time Frame: At 67 hours, data reported over the last 4 weeks ]
   Patient reported severity of certain symptoms over the last 4 weeks on a scale of 0 to 10 (bloating, abdominal discomfort, incomplete evacuation, straining and urgency). Higher score would mean worse (more symptoms) outcome.
7. Symptom Frequency Assessment (SFA) [ Time Frame: At 67 hours, data reported over the last 7 days ]
   Patients reported the number of complete BMs they had during the last week (minimum could be 0 and the maximum could be any number greater than 0). Higher/lower scores could be the better or worse outcome (e.g., 0 bowel movements all week would be a worse outcome but over 10 bowel movements would be worse as well), it just depends on the extent.
8. Hamilton Anxiety Rating Scale (HAM-A) [ Time Frame: At 4 weeks ]
   The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <7 indicates no or minimal severity, 8-14 is mild anxiety, 15-23 is moderate anxiety and 24 and worse is severe anxiety 5. Moderate-severe anxiety was defined as a score of 15 and above.
9. Beck's Depression Inventory (BDI) [ Time Frame: At 4 weeks ]
   Beck's Depression Inventory (BDI): is a 21-item tool assessing the existence and severity of symptoms of depression, as defined by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV; 1994). The items correspond to symptoms of depression and are a four-point scale for each item ranging from 0 to 3. They are summed to give a single BDI score between 0-63 (where higher results reflect more severe depression). Grades are 1-10: normal, 11-16: mild mood disturbance, 17-20: borderline clinical depression, 21-30: moderate depression, 31-40: severe depression, and >40 extreme depression 6. Moderate-severe depression was defined as a score of 21 and above.
10. Work Productivity and Activity Impairment (WPAI) [ Time Frame: At 7 days ]
    Work Productivity and Activity Impairment (WPAI): examines the effect of GI symptoms on loss of work time and loss of productivity. Patients indicated if they are unemployed. For employed patients, scores are presented as percentage of time lost during the last week (hours lost due to GI symptoms out of the hours that patient should have worked, excluding the time lost on participating in the study). Higher percentages indicate greater impairment. Work missed percentage, reduced productivity percentage, and work-productivity impairment percentage (combining the 2 scores) are calculated 7. We defined work/productivity impairment as either being unemployed or having lost 40% or more of work time or productivity. For employed patients, scores are presented as percentage of time lost during the last week (hours lost due to GI symptoms out of the hours that patient should have worked, excluding the time lost on participating in the study).
11. IBS Quality of Life (IBS QoL) and Sub-scores [ Time Frame: At 4 weeks ]
    Irritable bowel syndrome quality of life (IBS-QOL): Assesses bowel specific QOL. It consists of 34 items of a 5-point Likert scale. The total score is summed and then transformed to a 0-100 scale, where 0 is low QoL, and 100 is the best QoL. Different IBS-QOL items can also be categorized to eight subscale scores (Dysphoria, Interference with Activity, Body Image, Health Worry, Food Avoidance, Social Reaction, Sexual, Relationships). Note be made, that the IBS-QOL examines the effect of "bowel problems" on different aspect of QOL, and so was used to assess the effect of gut symptoms on the patients' QOL. Higher scores are better outcome.
12. Bristol Stool Scale [ Time Frame: At 7 days ]
    Bristol Stool Scale: patients indicate their last 7 days stool consistency on 1-7 visual scale. The Bristol stool scale correlates with colonic transit time. Higher scores do not indicate better or worse outcomes. It is a visual scale.

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

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

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

  Study Documents (Full-Text)

Documents provided by Braden Kuo, Massachusetts General Hospital:

Study Protocol and Statistical Analysis Plan  [PDF] August 31, 2017

More Information

• Responsible Party: Braden Kuo, Instructor in Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02798458
• Other Study ID Numbers: 2015P000097
• First Posted: June 14, 2016
• Results First Posted: March 27, 2023
• Last Update Posted: March 27, 2023
• Last Verified: February 2023

Keywords provided by Braden 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