Evolution of Albumin on AOA1 Patients Supplemented With Coenzyme Q10 (AOA1)

We propose a study on Ataxia with oculomotor apraxia type 1 (AOA1) in which Coenzyme Q10 (CoQ10) deficit has been observed. Main objectives of the study are :

• To monitor evolution of albumin in patients affected with AOA1 while supplemented with CoQ10 ;
• To measure with clinical scales and biological markers efficacy of supplementation on disease evolution.

AOA1 is characterised by Hypoalbuminemia. Disease duration is negatively correlated with albumin level. This study aims to understand mechanisms of the disease and our hypothesis is that correction or stabilization of albumin level with CoQ10 supplementation could impact disease evolution. The study is planned from 1 to 2 years supplementation. The CoQ10 is classified as a food supplement and has already been tested in other neurological conditions.

Study Overview

• Status: Completed
• Conditions: Ataxia-oculomotor Apraxia 1
• Intervention / Treatment: Dietary supplement: CoQ10; Other: Sanomit Placebo

Detailed Description

Ataxia with ocular apraxia type 1 (AOA1) is an autosomal recessive cerebellar ataxia. Patients' phenotype associates early onset cerebellar ataxia, oculomotor apraxia, neuropathy and often intellectual disability, hypoalbuminaemia and hypercholesterolemia.

APTX gene mutations responsible for AOA1 disease were identified in a family previously reported with ataxia and Coenzyme Q10 deficiency. Therefore we measured muscle Coenzyme Q10 in six patients AOA1 and found decreased levels in five. Hypercholesterolaemia and low albumin levels represent hallmarks of the disease.

We thus propose therapeutic trial with Coenzyme Q10 in AOA1 patients, by using albumin evolution as primary endpoint.

Moreover several secondary endpoints will be performed:

• clinical examination (SARA scale)
• quantitative assessments of the ataxia (with the calculation of the Composite Cerebellar Functional Severity CCFS)
• biological criteria (prealbumin, cholesterol, alphafoetoprotein, blood count, hepatic checkup)
• oculographic examination.

The study is a multicentric randomised placebo controlled trial with two-year follow-up:

• during the first year, one group will be supplemented with Coenzyme Q10 while the other group will receive a placebo;
• during the second year, all patients will be supplemented with Coenzyme Q10 in order to assess long term safety and tolerance of the treatment.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • ICM Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• 1. Diagnosis of ataxia with oculomotor apraxia type I (AOA1) confirmed by genetic molecular analysis
• 2. Age ≥ 18 years
• 3. Hypoalbuminemia
• 4. Efficient contraception for women of childbearing potential (with pregnancy test during each visit)
• 5. Signature of the written informed consent form
• 6. Presence of a support person (for patient with cognitive disorders)

Exclusion criteria :

• 1. Hypersensitivity to one of the excipients (glycerin, ethanol, lecithin)
• 2. Absence of hypoalbuminemia

• 3. During the 2 months before inclusion :

  • Use of CoQ10
  • Treatment with antioxidants (vitamin C) and statins
  • Use of drugs affecting mitochondrial activity
  • Anti-cholesterol, thyroid hormones, anti-arrhythmic compounds, warfarin, metformin or clozapine
• 4. Treatment with vitamin E, calcium, magnesium and/or other vitamins with a concentration superior to 149 UI during more than 3 months before inclusion
• 5. Use of drugs interfering with catacholamine metabolism (reserpine, amphetamine, or inhibitors of the monoamine oxidase A, methylphenidate, cinnarizine) during the month before inclusion
• 6. Non balanced treatment with anxiolytics, hypnotics, tranquillizers and/or antidepressants during the month before inclusion
• 7. Hypothyroidism with thyroxin use
• 8. Epilepsy
• 9. Psychotic disorders
• 10. Pregnancy or lactation period
• 11. Woman of childbearing potential without efficient contraception
• 12. Participant to other therapeutic studies during the month before inclusion
• 13. Inability to receive a clear information on the research
• 14. Inability to participate to the totality of the study
• 15. Non affiliation to social security (beneficiary or assignee)
• 16. Refusal of signing the consent form

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Coenzyme Q10 (CoQ10) - is a Dietary complement that contains Coenzyme Q10 (Ubidecarenone) well characterized nano particles.	Dietary supplement: CoQ10; • 2 dosages according to patient weight: Weight < 50kg : 20 drops 3 times a day (150 mg / d) Weight ≥ 50 kg : 40 drops 3 times a day (300 mg / d)
Placebo Comparator: 2; Placebo of CoQ10 is a translucent nano-emulsion of well characterized nano particles. Lecithin (and) Alcohol (and) Glycerin (and) Aqua	Other: Sanomit Placebo; • according to patient weight: Weight < 50kg : 20 drops 3 times a day Weight ≥ 50 kg : 40 drops 3 times a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Albuminemia	Evolution of albuminemia every 6 months during 2 years.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SARA scale	Evolution of clinical criteria (SARA and CCFS, which represent quantitative scales to assess cerebellar ataxia evolution)	2 years
CCFS	Evolution of clinical criteria (SARA and CCFS, which represent quantitative scales to assess cerebellar ataxia evolution)	2 years
prealbuminemia	Evolution of biological criteria (prealbuminemia, cholesterol, alfa-foeto-protein) every 6 months during 2 years.	2 years
cholesterol	Evolution of biological criteria (prealbuminemia, cholesterol, alfa-foeto-protein) every 6 months during 2 years.	2 years.
alfa-foeto-protein	Evolution of biological criteria (prealbuminemia, cholesterol, alfa-foeto-protein) every 6 months during 2 years.	2 years.
Oculomotor evaluation	Oculomotor evaluation to assess oculo motor apraxia evolution [Time Frame: Each year during 2 years.]	2 years
EQ5D - PHQ9	Quality of life evolution (self-administered questionnaire EQ5D - PHQ9) every 6 months during 2 years.	2 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Perrine Charles, MD, PhD, Assitance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: September 29, 2014
• First Submitted That Met QC Criteria: January 6, 2015
• First Posted (Estimate): January 7, 2015

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: November 3, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: CoQ10; hypoalbuminemia; Ataxia with Oculomotor Apraxia type 1
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Dyskinesias; Psychomotor Disorders; Vasculitis; Cranial Nerve Diseases; Vestibulocochlear Nerve Diseases; Ataxia; Apraxias; Cogan Syndrome; Physiological Effects of Drugs; Micronutrients; Vitamins; Coenzyme Q10
• Other Study ID Numbers: P081107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No