Digestive Dysmotility in Mitochondrial Neurogastrointestinal Encephalomyopathy

Recruiting

• Conditions: MNGIE; Dysmotility

• Registration Number: NCT05658822
• Lead Sponsor: Hospital Universitari Vall d'Hebron Research Institute

Brief Summary

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.

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 Timeline

• Study Start: 2018-02-01
• Status Verified: 2022-11
• Study First Submitted: 2022-11-27
• Study First Submitted QC: 2022-12-17
• Last Update Submitted: 2022-12-17
• Study First Posted: 2022-12-21
• Last Update Posted: 2022-12-21
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
intestinal motility at diagnosis	In patients included, in the first 30 days from diagnosis	to assess the amplitude (mmHg) of contractions during fasting and after nutrients measured by high-resolution intestinal manometry

Secondary Outcome Measures

Name	Time	Method
intestinal motility response to hepatic transplant	one and two years after hepatic transplant treatment	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

Trial Locations

Locations (1)

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain