Clinical trial with Phenilbutirrate to reduce lactic acid in patients affected with Melas Syndrome and PHD deficency encephalopathy
- Conditions
- Melas Syndrome and PDH deficency enchephalopathyMedDRA version: 20.0Level: PTClassification code 10053872Term: MELAS syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disordersMedDRA version: 20.0Level: LLTClassification code 10062950Term: Leigh syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-001094-25-IT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 9
The inclusion criteria are:
1.Age between 3 and 65 years old
2.Confirmed molecular diagnosis: mutations in PDHA1 and m.3 243A>G mtDNA point mutation
3.Plasma lactic acid =2100 umol/l (normal value . 580-2100)
4.Availability of brain MRI and MRSI at baseline (pre-treatment);
5.Availability of PDH residual activity in cultured fibroblasts in PDH1A patients at baseline (pre-treatment)
6.Written informed consent (and assent when applicable) obtained from subject or subject’s legal representative and ability for subject to comply with the requirements of the study.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1
The exclusion criteria will be:
1) Comorbidity with other chronic diseases.
2)Other experimental treatment in the previous 6 months.
3)Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
4)At Screening, the estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2.
5)At Screening presence of history of liver failure.
6)Subject has undergone an in-patient hospitalization within the 30 days prior to the Baseline Visit or has a planned hospitalization or a surgical procedure during the trial.
7)Subject has a history of active substance abuse during the year before the Baseline Visit, in the opinion of the Investigator.
8)Subject has any prior or current medical condition that, would prevent the subject from safely participating in and/or completing all trial requirements .
9) The patient will be excluded from the study if he presents a hart insufficiency ( FE < 40% ) severe renal failure (GRF GFR between 29 and 15 ml/min) clinical conditions in which sodium retention is found with edema, fructose intolerance, glucose / galactose malabsorption or saccharose or isomaltase enzyme deficiencies.
10)Hypersensitivity to the drug or to the excipients.
11)Not able to obtain written informed consent (and assent when applicable) from subject or subject’s legal representative and ability for subject to comply with the requirements of the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to investigate the efficiency and safety of PB in patients with PDH deficiency and MELAS .;Primary end point(s): The primary endpoint of the study is the reduction of lactic acidosis.;Timepoint(s) of evaluation of this end point: All along the trial;Secondary Objective: The secondary objectives are to identify novel biomarkers for these two diseases and to evaluate whether the clinical/biochemical efficacy detected in patients correlates with the response observed in the skin fibroblasts of PDH deficiency/MELAS patients and in cybrids from MELAS patients incubated with PB.
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: All along the trial;Secondary end point(s): A.Clinical efficiency of PB<br>B.To evaluate the biochemical efficiency of PB,