Evolution of Nutritional Status and Intestinal Function During the Course of the Disease in Patients With Mitochondrial Neurogastrointestinal Encephalomyopathy (Mitochondrial Neurogastrointestinal Encephalomyopathy; MNGIE)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Nutritional status 1
研究概览
简要总结
Mitochondrial neurogastrointestinal encephalomyopathy syndrome (MNGIE) is a rare disease characterized by severe gastrointestinal and neurological dysfunction. Its prevalence is 1-9 caIt is a genetic syndrome, with autosomal recessive inheritance, due to mutations in the nuclear gene TYMP (located on chromosome 22q13.32-qter) which encodes the protein thymidine phosphorylase (TP), an enzyme involved in the phosphorylation of the thymidine nucleoside. These mutations result in a significant reduction or complete absence of the enzyme's activity. There is therefore an increase in plasma levels of thymidine and its metabolites, thymidine nucleoside (dThd) and deoxyuridine (dUrd), with toxic accumulation both at a systemic and tissue level, which induces damage and depletion of mitochondrial DNA (mtDNA), multiple deletions and point mutationsses per 1000,000. It is included in the portal of rare diseases and orphan drugs. This syndrome is characterized by severe gastrointestinal and neurological disorders. Gastrointestinal symptoms are the main manifestation of the disease. They are present in 57% of cases at onset and in 100% of cases at diagnosis. Patients present with diarrhea, abdominal pain, borborygmi, vomiting, symptoms of intestinal pseudo-obstruction (32%-65% of cases), weight loss and cachexia (100% of cases). The symptoms, due to the progressive accumulation of metabolites toxic to mitochondrial DNA, are cumulative and evolutionary over time. The available therapeutic options (peritoneal dialysis, platelet infusion and enzyme replacement therapy) are unable to produce lasting clinical improvement. The drastic reduction in weight, resulting from the inability of patients to eat effectively orally, requires the use of home parenteral nutrition (NPD) in almost all cases.
The objective of the study is to describe the evolution of the nutritional status and intestinal function during the course of the disease in patients with MNGIE.
详细描述
This is a drug-free observational study, both retrospective and prospective, single-center carried out on adult patients with MNGIE, followed at the Regional Reference Center for Benign Chronic Intestinal Insufficiency-Pironi of the IRCCS-AOUBo based on data collected during clinical follow-up at the same centre. The data will be collected in a structured manner using the information present in the medical records obtained in the past as part of normal clinical practice for patients already in the care of the Center at the time of inclusion in the study and that obtained at the time of taking charge of the Center and during clinical follow-up, for new patients.
The study is an observational study without drug and does not involve any study-specific treatment or visit, but exclusively the structured collection of information obtained in the past as part of normal practice (clinical records and related documents) for the retrospective phase and the registration of clinical data collected during the normal care process (follow-up), for the prospective phase. The study does not include any study-specific visits The data will be collected at quarterly intervals starting from the moment the Center takes charge of the patients (time T0).
The following data relating to the history of the disease will also be collected: age at onset of symptoms, age at diagnosis, symptoms and signs at onset, symptoms and signs at diagnosis, symptoms and signs during clinical follow-up. The study population consists of patients with MNGIE followed at the SSD-Clinical Nutrition and Metabolism - Regional Reference Center for Benign Chronic Intestinal Insufficiency-Pironi of the AOU-Policlinico di Sant'Orsola.
MNGIE is a rare syndrome for which a prevalence of 1-9 cases per million inhabitants is described. In Italy there are about ten confirmed cases. To date, the Center has followed 8 patients with MNGIE, of which 6 are currently still in the care of the center and two have died.
It will also be necessary to use the data of patients who did not give consent because they had died or were no longer associated with our center, since failure to involve this population would reduce the eligible sample, producing negative consequences for the study in terms of the significance of the results. Therefore, in the case of deceased or untraceable patients following every reasonable effort made to contact them (via postal address, contact with the general practitioner or via telephone call but only in cases in which the patient had previously expressed consent to telephone contact ), on the basis of General Authorization no. 9 to the processing of personal data carried out for scientific research purposes, issued by the Guarantor on 11/12/2014, the processing of personal data will be carried out in the absence of consent.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of MNGIE (positive genetic investigation for the presence of mutation of the nuclear TYMP gene).
- •Obtaining informed consent
排除标准
- 未提供
结局指标
主要结局
Nutritional status 1
时间窗: at well being, at diagnosis of MNGIE, at FUP every four months, at last FUP/death
BMI
Nutritional status 2
时间窗: at well being, at diagnosis of MNGIE, at FUP every four months, at last FUP/death
Body composition by bioimpedance analysis when available
Nutritional status 3
时间窗: at well being, at diagnosis of MNGIE, at FUP every four months, at last FUP/death
Serum Albumin (mg/L) when available
次要结局
未报告次要终点