Evaluation of the Gastrointestinal Manifestation of Fabry's Disease

NCT ID: NCT02798458

Last Updated: 2023-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2022-11-30

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.

Conditions

Fabry's Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Smartpill

Intervention Type: DEVICE

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.

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

Group Type: EXPERIMENTAL

Smartpill

Intervention Type: DEVICE

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.

Endoscopic Mucosal Resection

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: DEVICE

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.

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Braden Kuo

Instructor in Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Braden Kuo, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

Bar N, Karaa A, Kiser K, Kuo B, Zar-Kessler C. Gastrointestinal Sensory Neuropathy and Dysmotility in Fabry Disease: Presentations and Effect on Patient's Quality of Life. Clin Transl Gastroenterol. 2023 Dec 1;14(12):e00633. doi: 10.14309/ctg.0000000000000633.

Reference Type: DERIVED

PMID: 37578052 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015P000097

Identifier Type: -

Identifier Source: org_study_id