Digestive Dysmotility in Mitochondrial Neurogastrointestinal Encephalomyopathy

Enteric Dysmotility in Mitochondrial Neurogastrointestinal Encephalomyopathy Patients Detected by High-resolution

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is an ultra-rare mitochondrial disease caused by mutations of the gen that codifies the enzyme thymidine phosphorylase The genetic defect results in systemic accumulation of the nucleosides thymidine and deoxyuridine. Clinically MNGIE is characterized by a combination of gastrointestinal and neurological manifestations, including severe gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoplegia and sensorimotor neuropathy. Gastrointestinal symptoms are the most frequent first manifestation of the disease, and include early satiety, nausea, dysphagia, postprandial emesis, abdominal pain, abdominal distention, and diarrhea. The disease is relentlessly progressive and the cause of death is primarily related to digestive dysmotility. However, the specific motor dysfunctions that produce the symptoms, i.e., the underlying mechanisms, remain uncertain.

Study Overview

• Status: Recruiting
• Conditions: MNGIE; Dysmotility

Detailed Description

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is an ultra-rare mitochondrial disease caused by mutations of the gen that codifies the enzyme thymidine phosphorylase The genetic defect results in systemic accumulation of the nucleosides thymidine and deoxyuridine. Clinically MNGIE is characterized by a combination of gastrointestinal and neurological manifestations, including severe gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoplegia and sensorimotor neuropathy. Gastrointestinal symptoms are the most frequent first manifestation of the disease, and include early satiety, nausea, dysphagia, postprandial emesis, abdominal pain, abdominal distention, and diarrhea. The disease is relentlessly progressive and the cause of death is primarily related to digestive dysmotility. However, the specific motor dysfunctions that produce the symptoms, i.e., the underlying mechanisms, remain uncertain, because so far, no studies on gastrointestinal motility in MNGIE have been published. The aims of this study were to identify the upper GI motor dysfunction in MNGIE patients, and to determine their relation to the clinical manifestations. Since the life-threatening consequences of the disease involve the upper gastrointestinal tract, all patients, after a thorough clinical and neurological evaluation, fulfilled a structured clinical questionnaire on digestive manifestations, and underwent state-of-the-art evaluation of the esophagus and the small bowel by high-resolution manometry (HRM), and gastric emptying by scintigraphy

• Study Type: Observational
• Enrollment (Anticipated): 6

Contacts and Locations

• Study Contact: Name: Carolina Malagelada, MD; Phone Number: +34932746259; Email: cmalagelada@vhebron.net
• Study Contact Backup: Name: Luis Alcala, MD; Phone Number: 34 695101188; Email: lgalcala1986@gmail.com

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with MNGIE

Description

Inclusion Criteria:

• diagnosis of MNGIE disease established by thymidine phosphorylase activity and mitochondrial mutation analysis.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intestinal motility at diagnosis	to assess the number of intestinal contractions (contractions per minute) during fasting and after the infusion of nutrients measured by high-resolution intestinal manometry	In patients included, in the first 30 days from diagnosis
intestinal motility at diagnosis	to assess the amplitude (mmHg) of contractions during fasting and after nutrients measured by high-resolution intestinal manometry	In patients included, in the first 30 days from diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intestinal motility response to hepatic transplant	to assess changes in the number of intestinal contractions (contractions per minute) during fasting and after the infusion of nutrients measured by high-resolution intestinal manometry after hepatic transplant	one and two years after hepatic transplant treatment
intestinal motility response to hepatic transplant	to assess the amplitude of intestinal contractions during fasting and after the infusion of Amplitude (mmHg) of contractions during fasting and after nutrients measured by high-resolution intestinal manometry after hepatic transplant	one and two years after hepatic transplant treatment

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: November 27, 2022
• First Submitted That Met QC Criteria: December 17, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 17, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: motility; Intestinal manometry
• Other Study ID Numbers: PR(AG)56/2018E

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No