Clinical Study of Hydroxytyrosol (HT) in Mitochondrial Diseases

NCT04543968 | Completed

• 1 other identifier: Clinical study of HT in MDs
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Mitochondrial Diseases

Keywords

mitochondria; mitochondrial diseases; MD; mitochondrial dysfunction; mitochondrial respiratory chain; MRC; oxidative phosphorylation; OXPHOS; mitochondrial

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (7)

• Change in blood gas parameter

  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

• Change in plasma lactate/pyruvate ratio

  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

• Change in plasma amino acid level

  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

• Change in urine organic acid level

  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

• Change in Paediatric Quality Of Life assessment: Paediatric Quality of Life Inventory version 4.0 generic core scale

  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

Study Arms (2)

hydroxytyrosol (HT) intake

EXPERIMENTAL

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

Dietary Supplement: hydroxytyrosol (HT) intake

hydroxytyrosol (HT) intake and withdraw

EXPERIMENTAL

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

Dietary Supplement: hydroxytyrosol (HT) intake and withdraw

Interventions

hydroxytyrosol (HT) intake DIETARY_SUPPLEMENT

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.

hydroxytyrosol (HT) intake

hydroxytyrosol (HT) intake and withdraw DIETARY_SUPPLEMENT

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.

hydroxytyrosol (HT) intake and withdraw

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hong Kong Children's Hospital: lead
• The University of Hong Kong: collaborator

Study Sites (1)

Hong Kong Children's Hospital

Hong Kong, Hong Kong

Location

Related Publications (7)

• 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.

  PMID: 27277220 BACKGROUND

• 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.

  PMID: 29074296 BACKGROUND

• 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.

  PMID: 31418093 BACKGROUND

• 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.

  PMID: 25503498 BACKGROUND

• 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.

  PMID: 20882356 BACKGROUND

• 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.

  PMID: 27865797 BACKGROUND

• 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.

  PMID: 15303006 BACKGROUND

Related Links

• The detailed development, testing, manual and final version of International Paediatric Mitochondrial Disease Score (IPMDS)
• Paediatric Quality of Life Inventory version 4.0 generic core scale (PedsQL 4.0 generic)
• Safety of hydroxytyrosol as a novel food pursuant to Regulation (EC) No 258/97. EFSA Journal 2017;15(3):4728
• GRAS Notice, GRN No. 876. Hydroxytyrosol 2019

MeSH Terms

Conditions

Mitochondrial Diseases

Interventions

3,4-dihydroxyphenylethanol

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Cheuk Wing Fung

  Hong Kong Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant

Model Details: 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.

Study Record Dates

• First Submitted: July 31, 2020
• First Posted: September 10, 2020
• Study Start: July 5, 2022
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: November 6, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)