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Clinical Study of Hydroxytyrosol (HT) in Mitochondrial Diseases

Primary Purpose

Mitochondrial Diseases

Status
Recruiting
Phase
Not Applicable
Locations
Hong Kong
Study Type
Interventional
Intervention
hydroxytyrosol (HT) intake
hydroxytyrosol (HT) intake and withdraw
Sponsored by
Hong Kong Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mitochondrial Diseases focused on measuring mitochondria, mitochondrial diseases, MD, mitochondrial dysfunction, mitochondrial respiratory chain, MRC, oxidative phosphorylation, OXPHOS, mitochondrial

Eligibility Criteria

3 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

  1. Subject (aged 3-18 years) is confirmed to have pathogenic MD-associated nuclear DNA or mtDNA mutations.
  2. Subject is willing and able to comply with all requirements of the clinical trial.
  3. Subject is given enough time and opportunity to consider his/her participation and has signed his/her written consent.

Exclusion criteria

  1. Subject is participating or has participated within the last 2 months in any clinical trial involving hydroxytyrosol (HT) or hydroxytyrosol (HT) -associated phenols as dietary supplements.
  2. Subject has a medical condition which can be exacerbated by hydroxytyrosol (HT) or hydroxytyrosol (HT) -associated phenols.
  3. Subject has allergy to olive oil.
  4. Subject is pregnant.

Sites / Locations

  • Hong Kong Children's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

hydroxytyrosol (HT) intake

hydroxytyrosol (HT) intake and withdraw

Arm Description

MD patients will receive hydroxytyrosol (HT) daily as dietary supplements for 12 months. After that, patients will be randomly assigned in 1:1 ratio to continue on receiving hydroxytyrosol (HT) as their dietary supplements for another 6 months. Doses of hydroxytyrosol (HT) intake: (1) 3-10 years old, 10 mg/day; (2) 11-18 years old 30mg/day

MD patients will receive hydroxytyrosol (HT) daily as dietary supplements for 12 months. After that, patients will be randomly assigned in 1:1 ratio to withdraw from receiving hydroxytyrosol (HT) as their dietary supplements for another 6 months. Doses of hydroxytyrosol (HT) intake: (1) 3-10 years old, 10 mg/day; (2) 11-18 years old 30mg/day

Outcomes

Primary Outcome Measures

Change in International Paediatric Mitochondrial Disease Score
International Paediatric Mitochondrial Disease Score was previously established by Radboud Centre for Mitochondrial Medicine to monitor symptoms and signs of disease progression in MD patients aged from 1-18 years old. This scale was suggested to be a robust tool for the follow-up of children with MD and aimed for the purpose in clinical trials. International Paediatric Mitochondrial Disease Score consists of 61 items in 3 domains (Domain 1, 2 and 3). Domain 1 has 23 items providing the detailed insights into subjective complaints and symptoms which should be assessed by interviewing parents or caregivers. Domain 2 consists of 25 items assessed by physical examination. Domain 3 has 13 items of functional assessment obtained by physical/motor function evaluation. Minimum value of raw score is 0 and maximum value is 243. Lower score means better clinical status.

Secondary Outcome Measures

Change in blood gas parameter
Blood gases will be measured by electrochemical analysis which can reveal metabolic acidosis acting as one of the indicators for MD.
Change in plasma lactate/pyruvate ratio
Plasma lactate/ pyruvate will be measured by automated enzymatic method and marked elevation of plasma lactate/ pyruvate ratio suggests the presence of mitochondrial dysfunction because of a shift in mitochondrial redox state.
Change in plasma amino acid level
Plasma amino acids will be measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Increase in plasma amino acid level including alanine, glycine, proline and threonine will indicate an alteration of redox state caused by respiratory chain dysfunction.
Change in urine organic acid level
Urine organic acid will be measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Urine organic acid analysis can showed elevation of malate, fumarate, 3-methylglutaconic acid etc, in MD patients.
Change in Paediatric Quality Of Life assessment: Paediatric Quality of Life Inventory version 4.0 generic core scale
The measurement model the investigators will use will be the Paediatric Quality of Life Inventory version 4.0 generic core scale for the measurement of health-related quality of life in children and adolescents who are healthy or with acute and chronic health condition. Paediatric Quality Of Life assessment consists of 5 versions of the same questionnaire for various age ranges: a) toddler version for 2-4 year old; b) young child version for 5-7 years old; c) child version for 8-12 years old; d) adolescent version for 13-18 years old; e) young adult version for 18-23 years old. Each of the versions has a parent version for proxy report and child version for self-report (except for the toddler version). Each version is composed of 23 items with 4 scales (physical, emotional, social and school functioning) and 3 summary scores (total, physical health summary, psychosocial health summary score). The scale scores ranged from 0-100 and higher score indicates better quality of life.
Study of tolerability of hydroxytyrosol (HT): number of intervention-related adverse events
The MD patients will be followed up by a clinician during the time of functional assessment. The tolerability will be assessed by evaluating the number of intervention-related adverse events in patients taking hydroxytyrosol (HT) as dietary supplements. Adverse events were not reported in the literature but may potentially include gastrointestinal upset, vomiting, nausea, and diarrhea with subsequent weight loss.
Change in radiological evaluation
Magnetic resonance imaging of the brain with spectroscopy will be used to evaluate patients' responses before the trial as baseline, 12 months after receiving EVOO and 6 months after withdrawal or being maintained on EVOO after randomization. Radboud Centre for Mitochondrial Medicine Pediatric MRI score (RCMM-PMRIS), will be used for the outcome measure. RCMM-PMRIS focuses on 6 most commonly described abnormalities in neuroimaging and define the extent of brain involvement. This can help to evaluate MD severity, disease progression and effect of treatment radiologically.

Full Information

First Posted
July 31, 2020
Last Updated
July 13, 2022
Sponsor
Hong Kong Children's Hospital
Collaborators
The University of Hong Kong
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1. Study Identification

Unique Protocol Identification Number
NCT04543968
Brief Title
Clinical Study of Hydroxytyrosol (HT) in Mitochondrial Diseases
Official Title
Open Label Pilot Study Using Hydroxytyrosol (HT) as a Dietary Supplement in Patients With Mitochondrial Diseases (MDs)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 5, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hong Kong Children's Hospital
Collaborators
The University of Hong Kong

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Mitochondrial diseases (MDs) are the commonest group of inborn errors resulting from primary dysfunction of mitochondrial respiratory chain (MRC). High phenolics-containing extra-virgin olive oil (EVOO) can be one of the potential dietary supplements for the treatment of MD. Previous reports demonstrated that phenolics including oleuropein, oleocanthal, hydroxytyrosol and tyrosol found in EVOO have strong antioxidant properties against the oxidative stress in brain tissue and showed a protective effect on mitochondria by restoring mitochondrial enzymatic activities. This proposed study is an open-label pilot/ feasibility clinical trial using hydroxytyrosol (HT) as dietary supplements in a cohort of 12 MD patients recruited from the Hong Kong Children's Hospital (HKCH). The objective is to explore the longitudinal effect of receiving hydroxytyrosol (HT) as dietary supplements over a 12-month period and the change on a 6-month period after withdrawal. The applicability of the outcome measures will be evaluated in the current trial for future clinical studies and obtain relevant data for the next phase of the clinical trial on hydroxytyrosol (HT) efficacy. Besides, the tolerability of hydroxytyrosol (HT) in MD patients will be evaluated. The primary outcome measure is the functional assessment of the patient's clinical outcomes by International Paediatric Mitochondrial Disease Score (IPMDS). Secondary outcome measures included the measurement of biochemical and radiological parameters. Besides, tolerability and quality of life of the subjects will be determined. Relevant data including the feasibility of subject recruitment, withdrawal rate, feasibility of data collection of outcome measures, longitudinal effect of hydroxytyrosol (HT) on the outcome measures in the trial can be collected and analysed in this pilot study providing important information for the future clinical trials. The ultimate goal is to develop effective therapies to lower mortality, improve the clinical outcomes and quality of life in MD patients.
Detailed Description
High phenolics-containing extra-virgin olive oil (EVOO) can be one of the potential dietary supplements for the treatment of MD. There is growing evidence to suggest that daily consumption of EVOO in Mediterranean diets have beneficial effects on preventing neurodegeneration. Previous reports demonstrated that phenolics including oleuropein, oleocanthal, hydroxytyrosol and tyrosol found in EVOO have strong antioxidant properties against the oxidative stress in brain tissue and protective effect on both acute and chronic neurodegenerative diseases by in vitro study and animal models. In addition to improvement of arsenic-induced oxidative stress by oleuropein or hydroxytyrosol treatment, hydroxytyrosol also showed a protective effect on mitochondria by restoring mitochondrial enzymatic activities in rat brain. In vitro study also demonstrated the stimulatory effect of hydroxytyrosol on mitochondrial function including in mouse 3T3-L1 adipocytes and human endothelial cells. A recent reported clinical study showed that consumption of olive oil could increase mitochondrial membrane fluidity and ATPase activity in patients with relapsing-remitting multiple sclerosis, a neurodegenerative disease associated with mitochondrial dysfunction. Mitochondrial diseases (MDs) are the commonest group of inborn errors with a minimal prevalence of 12.5 per 100,000 and 4.7 per 100,000 adults and children respectively. These diseases are resulted from primary dysfunction of mitochondrial respiratory chain (MRC) which is mostly caused by both nuclear and mitochondrial DNA defects. They are progressive, multisystem disorders that can affect many parts of the body including brain, nerve, muscle, kidney, heart, liver, eyes, ears or pancreas and some are devastating or even life threatening. Development of effective treatments for the patients is an unmet need until now. Effective treatment strategies and clinical trials are limited, and therapies are mostly palliative. Drug developments and clinical trials for these diseases are scarce in Hong Kong when compared with other countries. MDs are extremely heterogeneous phenotypically and genetically with the biochemical dysfunction and pathogenic mechanisms being unique in each individual molecular defect. With the advance in next generation sequencing, over 300 mitochondrial genes are implicated to cause human diseases. This wide heterogeneity has been hindering the development of new therapeutic strategies such as gene therapy which requires long term evaluation and substantial manipulation to improve efficacy and reduce toxicity risk. It is therefore not efficient nor realistic to develop unique therapy targeting at a specific molecular defect. The future pharmaceutical development for treating mitochondrial dysfunctions will focus on boosting the residual mitochondrial function by non-specific bypassing the defective components of MRC or improving the aberrant cellular consequences. Dietary supplements were demonstrated to treat MD owing to their roles as metabolic cofactors to ameliorate mitochondrial ATP production, bypass mitochondrial complex defects and remove toxic metabolites. However, there are few randomized controlled trials to assess the cause-effect relationship of these dietary supplements. The present study is a feasibility clinical trial to explore the longitudinal effect of receiving hydroxytyrosol (HT) as dietary supplements on primary and secondary outcomes (clinical, biochemical and radiological parameters and quality of life) and tolerability in MD patients in Hong Kong. The investigators aim to obtain relevant data to determine the sample size and treatment duration for the next phase of the clinical trial on hydroxytyrosol (HT) efficacy. Another aim of this study is to evaluate the applicability of the outcome measures in the current study for future clinical trials on different treatment strategies. This pilot study will be a longitudinal, open label study. Twelve subjects will be recruited, including MD patients with confirmed MD-associated nuclear DNA or mtDNA mutations, from the Hong Kong Children's Hospital (HKCH). Subjects will receive hydroxytyrosol (HT) daily as dietary supplements for 12 months. After that, patients will be randomly assigned in 1:1 ratio to either continue on or withdraw from receiving hydroxytyrosol (HT) as their dietary supplements for another 6 months. Hydroxytyrosol (HT) dosage are based on the past clinical trials in humans and the NOAEL. The willingness of the participants to stay in the trial in terms of the percentage of participants completing the whole trial on hydroxytyrosol (HT) dietary supplement will be assessed. The withdrawal rate in different study periods and the reasons of withdrawal will be further studied. Subjects will visit the trial site at different time points after the start of dietary supplements for clinical follow up, functional assessment including questionnaire, blood and urine sampling and neuroimaging as primary and secondary outcome measures. There will be more frequent follow-up and monitoring after initiation and withdrawal of supplements. Data of primary and secondary outcome measures (except radiological evaluation) will be collected before the trial as baseline, 2 weeks, 6 weeks, 3, 6, 9, 12 months after the commencement of the trial and 2 weeks, 6 weeks, 3 and 6 months after randomization. The investigators will examine the feasibility of collecting data on the primary and secondary outcome measures in a clinical trial condition. The amount of missing data, the reason for the missing and difficulties on those data collection will be evaluated. An open label trial is used for this proposed study because a matching placebo with the same properties, such as taste, smell, colour, etc, as hydroxytyrosol (HT) to keep blindness is not yet developed at this moment. Therefore, a withdrawal design will be used even though this can be a limitation of this study because of the easy accessibility of hydroxytyrosol (HT) by the patients who can continue to use EVOO on their own after being assigned for withdrawal, which may potentially affect the outcome. Information on any deviation from the study protocol on this issue can be collected from the patients by questionnaires at the end of the study to guide the data analysis and interpretation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mitochondrial Diseases
Keywords
mitochondria, mitochondrial diseases, MD, mitochondrial dysfunction, mitochondrial respiratory chain, MRC, oxidative phosphorylation, OXPHOS, mitochondrial

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Twelve subjects will be recruited, including MD patients with confirmed MD-associated nuclear DNA or mtDNA mutations. Subjects will receive hydroxytyrosol (HT) daily as dietary supplements for 12 months. After that, patients will be randomly assigned in 1:1 ratio to either continue on or withdraw from receiving hydroxytyrosol (HT) as their dietary supplements for another 6 months.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
hydroxytyrosol (HT) intake
Arm Type
Experimental
Arm Description
MD patients will receive hydroxytyrosol (HT) daily as dietary supplements for 12 months. After that, patients will be randomly assigned in 1:1 ratio to continue on receiving hydroxytyrosol (HT) as their dietary supplements for another 6 months. Doses of hydroxytyrosol (HT) intake: (1) 3-10 years old, 10 mg/day; (2) 11-18 years old 30mg/day
Arm Title
hydroxytyrosol (HT) intake and withdraw
Arm Type
Experimental
Arm Description
MD patients will receive hydroxytyrosol (HT) daily as dietary supplements for 12 months. After that, patients will be randomly assigned in 1:1 ratio to withdraw from receiving hydroxytyrosol (HT) as their dietary supplements for another 6 months. Doses of hydroxytyrosol (HT) intake: (1) 3-10 years old, 10 mg/day; (2) 11-18 years old 30mg/day
Intervention Type
Dietary Supplement
Intervention Name(s)
hydroxytyrosol (HT) intake
Intervention Description
MD patients will receive hydroxytyrosol (HT) daily as dietary supplements for 12 months. After that, patients will be randomly assigned in 1:1 ratio to continue on receiving hydroxytyrosol (HT) as their dietary supplements for another 6 months.
Intervention Type
Dietary Supplement
Intervention Name(s)
hydroxytyrosol (HT) intake and withdraw
Intervention Description
MD patients will receive hydroxytyrosol (HT) daily as dietary supplements for 12 months. After that, patients will be randomly assigned in 1:1 ratio to withdraw from receiving hydroxytyrosol (HT) as their dietary supplements for another 6 months.
Primary Outcome Measure Information:
Title
Change in International Paediatric Mitochondrial Disease Score
Description
International Paediatric Mitochondrial Disease Score was previously established by Radboud Centre for Mitochondrial Medicine to monitor symptoms and signs of disease progression in MD patients aged from 1-18 years old. This scale was suggested to be a robust tool for the follow-up of children with MD and aimed for the purpose in clinical trials. International Paediatric Mitochondrial Disease Score consists of 61 items in 3 domains (Domain 1, 2 and 3). Domain 1 has 23 items providing the detailed insights into subjective complaints and symptoms which should be assessed by interviewing parents or caregivers. Domain 2 consists of 25 items assessed by physical examination. Domain 3 has 13 items of functional assessment obtained by physical/motor function evaluation. Minimum value of raw score is 0 and maximum value is 243. Lower score means better clinical status.
Time Frame
baseline, 2 weeks, 6 weeks, 3, 6, 9, 12 months after the commencement of the trial and 2 weeks, 6 weeks, 3 and 6 months after randomization
Secondary Outcome Measure Information:
Title
Change in blood gas parameter
Description
Blood gases will be measured by electrochemical analysis which can reveal metabolic acidosis acting as one of the indicators for MD.
Time Frame
Baseline, 2 weeks, 6 weeks, 3, 6, 9, 12 months after the commencement of the trial and 2 weeks, 6 weeks, 3 and 6 months after randomization
Title
Change in plasma lactate/pyruvate ratio
Description
Plasma lactate/ pyruvate will be measured by automated enzymatic method and marked elevation of plasma lactate/ pyruvate ratio suggests the presence of mitochondrial dysfunction because of a shift in mitochondrial redox state.
Time Frame
Baseline, 2 weeks, 6 weeks, 3, 6, 9, 12 months after the commencement of the trial and 2 weeks, 6 weeks, 3 and 6 months after randomization
Title
Change in plasma amino acid level
Description
Plasma amino acids will be measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Increase in plasma amino acid level including alanine, glycine, proline and threonine will indicate an alteration of redox state caused by respiratory chain dysfunction.
Time Frame
Baseline, 2 weeks, 6 weeks, 3, 6, 9, 12 months after the commencement of the trial and 2 weeks, 6 weeks, 3 and 6 months after randomization
Title
Change in urine organic acid level
Description
Urine organic acid will be measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Urine organic acid analysis can showed elevation of malate, fumarate, 3-methylglutaconic acid etc, in MD patients.
Time Frame
Baseline, 2 weeks, 6 weeks, 3, 6, 9, 12 months after the commencement of the trial and 2 weeks, 6 weeks, 3 and 6 months after randomization
Title
Change in Paediatric Quality Of Life assessment: Paediatric Quality of Life Inventory version 4.0 generic core scale
Description
The measurement model the investigators will use will be the Paediatric Quality of Life Inventory version 4.0 generic core scale for the measurement of health-related quality of life in children and adolescents who are healthy or with acute and chronic health condition. Paediatric Quality Of Life assessment consists of 5 versions of the same questionnaire for various age ranges: a) toddler version for 2-4 year old; b) young child version for 5-7 years old; c) child version for 8-12 years old; d) adolescent version for 13-18 years old; e) young adult version for 18-23 years old. Each of the versions has a parent version for proxy report and child version for self-report (except for the toddler version). Each version is composed of 23 items with 4 scales (physical, emotional, social and school functioning) and 3 summary scores (total, physical health summary, psychosocial health summary score). The scale scores ranged from 0-100 and higher score indicates better quality of life.
Time Frame
Baseline, 2 weeks, 6 weeks, 3, 6, 9, 12 months after the commencement of the trial and 2 weeks, 6 weeks, 3 and 6 months after randomization
Title
Study of tolerability of hydroxytyrosol (HT): number of intervention-related adverse events
Description
The MD patients will be followed up by a clinician during the time of functional assessment. The tolerability will be assessed by evaluating the number of intervention-related adverse events in patients taking hydroxytyrosol (HT) as dietary supplements. Adverse events were not reported in the literature but may potentially include gastrointestinal upset, vomiting, nausea, and diarrhea with subsequent weight loss.
Time Frame
Baseline, 2 weeks, 6 weeks, 3, 6, 9, 12 months after the commencement of the trial and 2 weeks, 6 weeks, 3 and 6 months after randomization
Title
Change in radiological evaluation
Description
Magnetic resonance imaging of the brain with spectroscopy will be used to evaluate patients' responses before the trial as baseline, 12 months after receiving EVOO and 6 months after withdrawal or being maintained on EVOO after randomization. Radboud Centre for Mitochondrial Medicine Pediatric MRI score (RCMM-PMRIS), will be used for the outcome measure. RCMM-PMRIS focuses on 6 most commonly described abnormalities in neuroimaging and define the extent of brain involvement. This can help to evaluate MD severity, disease progression and effect of treatment radiologically.
Time Frame
Baseline, 12 months after receiving hydroxytyrosol (HT) and 6 months after withdrawal or being maintained on hydroxytyrosol (HT) after randomization.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria Subject (aged 3-18 years) is confirmed to have pathogenic MD-associated nuclear DNA or mtDNA mutations. Subject is willing and able to comply with all requirements of the clinical trial. Subject is given enough time and opportunity to consider his/her participation and has signed his/her written consent. Exclusion criteria Subject is participating or has participated within the last 2 months in any clinical trial involving hydroxytyrosol (HT) or hydroxytyrosol (HT) -associated phenols as dietary supplements. Subject has a medical condition which can be exacerbated by hydroxytyrosol (HT) or hydroxytyrosol (HT) -associated phenols. Subject has allergy to olive oil. Subject is pregnant.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cheuk Wing Fung
Phone
852-5741 3216 (Secretary)
Email
fungcw@ha.org.hk
First Name & Middle Initial & Last Name or Official Title & Degree
Vanessa Chu
Email
vchu@hku.hk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cheuk Wing Fung
Organizational Affiliation
Hong Kong Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hong Kong Children's Hospital
City
Hong Kong
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheuk Wing Fung, MB,BS
Email
fungcw@ha.org.hk

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27277220
Citation
Koene S, Hendriks JCM, Dirks I, de Boer L, de Vries MC, Janssen MCH, Smuts I, Fung CW, Wong VCN, de Coo IRFM, Vill K, Stendel C, Klopstock T, Falk MJ, McCormick EM, McFarland R, de Groot IJM, Smeitink JAM. International Paediatric Mitochondrial Disease Scale. J Inherit Metab Dis. 2016 Sep;39(5):705-712. doi: 10.1007/s10545-016-9948-7. Epub 2016 Jun 9. Erratum In: J Inherit Metab Dis. 2017 May;40(3):463.
Results Reference
background
PubMed Identifier
29074296
Citation
Mancuso M, McFarland R, Klopstock T, Hirano M; consortium on Trial Readiness in Mitochondrial Myopathies. International Workshop:: Outcome measures and clinical trial readiness in primary mitochondrial myopathies in children and adults. Consensus recommendations. 16-18 November 2016, Rome, Italy. Neuromuscul Disord. 2017 Dec;27(12):1126-1137. doi: 10.1016/j.nmd.2017.08.006. Epub 2017 Sep 8. No abstract available.
Results Reference
background
PubMed Identifier
31418093
Citation
Jung B, Martinez M, Claessens YE, Darmon M, Klouche K, Lautrette A, Levraut J, Maury E, Oberlin M, Terzi N, Viglino D, Yordanov Y, Claret PG, Bige N; Societe de Reanimation de Langue Francaise (SRLF); Societe Francaise de Medecine d'Urgence (SFMU). Diagnosis and management of metabolic acidosis: guidelines from a French expert panel. Ann Intensive Care. 2019 Aug 15;9(1):92. doi: 10.1186/s13613-019-0563-2.
Results Reference
background
PubMed Identifier
25503498
Citation
Parikh S, Goldstein A, Koenig MK, Scaglia F, Enns GM, Saneto R, Anselm I, Cohen BH, Falk MJ, Greene C, Gropman AL, Haas R, Hirano M, Morgan P, Sims K, Tarnopolsky M, Van Hove JL, Wolfe L, DiMauro S. Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2015 Sep;17(9):689-701. doi: 10.1038/gim.2014.177. Epub 2014 Dec 11.
Results Reference
background
PubMed Identifier
20882356
Citation
Yang X, Xiao N, Yan J. The PedsQL in pediatric cerebral palsy: reliability and validity of the Chinese version pediatric quality of life inventory 4.0 generic core scales and 3.0 cerebral palsy module. Qual Life Res. 2011 Mar;20(2):243-52. doi: 10.1007/s11136-010-9751-0. Epub 2010 Sep 30. Erratum In: Qual Life Res. 2011 Mar;20(2):253.
Results Reference
background
PubMed Identifier
27865797
Citation
Wong SS, Goraj B, Fung CW, Vister J, de Boer L, Koene S, Smeitink J. Radboud Centre for Mitochondrial Medicine Pediatric MRI score. Mitochondrion. 2017 Jan;32:36-41. doi: 10.1016/j.mito.2016.11.008. Epub 2016 Nov 16.
Results Reference
background
PubMed Identifier
15303006
Citation
Panetta J, Smith LJ, Boneh A. Effect of high-dose vitamins, coenzyme Q and high-fat diet in paediatric patients with mitochondrial diseases. J Inherit Metab Dis. 2004;27(4):487-98. doi: 10.1023/B:BOLI.0000037354.66587.38.
Results Reference
background
Links:
URL
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987390/
Description
The detailed development, testing, manual and final version of International Paediatric Mitochondrial Disease Score (IPMDS)
URL
https://www.pedsql.org/
Description
Paediatric Quality of Life Inventory version 4.0 generic core scale (PedsQL 4.0 generic)
URL
https://www.efsa.europa.eu/en/efsajournal/pub/4728
Description
Safety of hydroxytyrosol as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal 2017;15(3):4728
URL
https://www.fda.gov/media/134474/download
Description
GRAS Notice, GRN No. 876. Hydroxytyrosol 2019

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Clinical Study of Hydroxytyrosol (HT) in Mitochondrial Diseases

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