Q10 Ubiquinol in Autism Spectrum Disorder and in Phelan-McDermid Syndrome.

NCT04312152 | Unknown

• 1 other identifier: Q10_study_ASD
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This double-blind, cross-over, randomized, controlled trial (RCT) has the aim of evaluating the effectiveness of a metabolic support therapy in two cohorts of patients with idiopathic Autism Spectrum Disorder or Phelan-McDermid syndrome, commonly associated with syndromic autism. Each patient will receive Q10 ubiquinol + Vit. E and B for 4 months and only Vit. E and B for 4 months in a double-blind, cross-over design. Primary outcome measures of efficacy include Vineland Adaptive Behavior Scales, Childhood Autism Rating Scale, Clinical Global Impression-Improvement and Visual Analog Scales; secondary outcome measures include several questionnaires and tests of autism, cognitive function, problem behaviors, quality of life, communication and comorbid disorders, as well as measures of oxidative stress.

Conditions

Autism Spectrum Disorder; Phelan-McDermid Syndrome

Keywords

Ubiquinol-10; Coenzyme Q10; Autism; Mitochondria; Oxidative stress; Cognitive symptoms; Chromosome 22q13 3 deletion syndrome

Outcome Measures

Primary Outcomes (4)

• Change in Vineland Adaptive Behavior Scales scores

  The Vineland Adaptive Behavior Scales are a standardized semi-structured interview to measure adaptive behavior, among the most sensitive to change in autism research. Standard scores have a mean of 100 and a standard deviation of 15.

  At 0, 4 and 8 months (pre- and post-treatment after each arm)

• Change in Childhood Autism Rating Scale score

  The Childhood Autism Rating Scale is a clinical rating scale for the trained clinician to rate the presence and severity of signs and symptoms of ASD by direct observation of the child. Scores can range from 15 to 60: below 30, non-autistic; 30-36.5, mild to moderate autism; 37-60, severe autism.

  At 0, 4 and 8 months (pre- and post-treatment after each arm)

• Change in Clinical Global Impression of Improvement scale scores between experimental and active comparator arms.

  The Clinical Global Impression of Improvement scale is a 7 point scale for the clinician to quantify illness severity, patient improvement/worsening and treatment side effects. Scores recorded at the end of the experimental and active comparator arms will be contrasted within-subject.

  4 and 8 months (record once at the end of each arm)

• Change in Visual Analog Scales scores

  16 visual analog scales have been created to measure all DSM-5 items included in the ASD diagnosis, as well as other cognitive and motor functions often affected in ASD. Scores measure the increasing severity of signs and symptoms on a 0-10 scale.

  At 0, 4 and 8 months (pre- and post-treatment after each arm)

Secondary Outcomes (13)

• Children's Global Assessment Scale

  At 0, 4 and 8 months (pre- and post-treatment after each arm)

• Social Responsiveness Scale

  At 0, 4 and 8 months (pre- and post-treatment after each arm)

• Repetitive Behaviors Scale - Revised

  At 0, 4 and 8 months (pre- and post-treatment after each arm)

• Aberrant Behavior Checklist

  At 0, 4 and 8 months (pre- and post-treatment after each arm)

• Short Sensory Profile

  At 0, 4 and 8 months (pre- and post-treatment after each arm)

Study Arms (4)

PMS Placebo

ACTIVE COMPARATOR

If body weight is up to 20 kg: * Vitamin E 30 mg b.i.d. * Multivitamin B complex b.i.d., including Vit. B1 (1.05 mg), Vit. B2 (1.2 mg), Niacin (9 mg), Pantothenic acid (4.5 mg), Vit. B6 (1.5 mg), Vit. B12 (4.5 mcg), Folic acid (0.1 mg), Biotin (0.1125 mg) If body weight is above 20 kg: * Vitamin E 30 mg b.i.d. * Multivitamin B complex b.i.d., including Vit. B1 (2.1 mg), Vit. B2 (2.4 mg), Niacin (18 mg), Pantothenic acid (9 mg), Vit. B6 (3 mg), Vit. B12 (9 mcg), Folic acid (0.2 mg), Biotin (0.225 mg)

Dietary Supplement: Vitamin E; Dietary Supplement: Multi-Vitamin B complex

ASD Placebo

ACTIVE COMPARATOR

If body weight is up to 20 kg: * Vitamin E 30 mg b.i.d. * Multivitamin B complex b.i.d., including Vit. B1 (1.05 mg), Vit. B2 (1.2 mg), Niacin (9 mg), Pantothenic acid (4.5 mg), Vit. B6 (1.5 mg), Vit. B12 (4.5 mcg), Folic acid (0.1 mg), Biotin (0.1125 mg) If body weight is above 20 kg: * Vitamin E 30 mg b.i.d. * Multivitamin B complex b.i.d., including Vit. B1 (2.1 mg), Vit. B2 (2.4 mg), Niacin (18 mg), Pantothenic acid (9 mg), Vit. B6 (3 mg), Vit. B12 (9 mcg), Folic acid (0.2 mg), Biotin (0.225 mg)

Dietary Supplement: Vitamin E; Dietary Supplement: Multi-Vitamin B complex

PMS Active compound

EXPERIMENTAL

If body weight is up to 20 kg: * Q10 ubiquinol, 50 mg b.i.d. * Vitamin E 30 mg b.i.d. * Multivitamin B complex b.i.d., including Vit. B1 (1.05 mg), Vit. B2 (1.2 mg), Niacin (9 mg), Pantothenic acid (4.5 mg), Vit. B6 (1.5 mg), Vit. B12 (4.5 mcg), Folic acid (0.1 mg), Biotin (0.1125 mg) If body weight is above 20 kg: * Q10 ubiquinol, 100 mg b.i.d. * Vitamin E 30 mg b.i.d. * Multivitamin B complex b.i.d., including Vit. B1 (2.1 mg), Vit. B2 (2.4 mg), Niacin (18 mg), Pantothenic acid (9 mg), Vit. B6 (3 mg), Vit. B12 (9 mcg), Folic acid (0.2 mg), Biotin (0.225 mg)

Dietary Supplement: Q10 Ubiquinol; Dietary Supplement: Vitamin E; Dietary Supplement: Multi-Vitamin B complex

ASD Active compound

EXPERIMENTAL

If body weight is up to 20 kg: * Q10 ubiquinol, 50 mg b.i.d. * Vitamin E 30 mg b.i.d. * Multivitamin B complex b.i.d., including Vit. B1 (1.05 mg), Vit. B2 (1.2 mg), Niacin (9 mg), Pantothenic acid (4.5 mg), Vit. B6 (1.5 mg), Vit. B12 (4.5 mcg), Folic acid (0.1 mg), Biotin (0.1125 mg) If body weight is above 20 kg: * Q10 ubiquinol, 100 mg b.i.d. * Vitamin E 30 mg b.i.d. * Multivitamin B complex b.i.d., including Vit. B1 (2.1 mg), Vit. B2 (2.4 mg), Niacin (18 mg), Pantothenic acid (9 mg), Vit. B6 (3 mg), Vit. B12 (9 mcg), Folic acid (0.2 mg), Biotin (0.225 mg)

Dietary Supplement: Q10 Ubiquinol; Dietary Supplement: Vitamin E; Dietary Supplement: Multi-Vitamin B complex

Interventions

Q10 Ubiquinol DIETARY_SUPPLEMENT

Q10 Ubiquinol (50 or 100 mg b.i.d. depending on body weight) in capsules containing also Vit. E and Vit. B complex, as described above. Capsules can be opened and the content drunk or chewed, if children have difficulties with swallowing capsules.

ASD Active compound; PMS Active compound

Vitamin E DIETARY_SUPPLEMENT

Vitamin E (30 mg b.i.d. regardless of body weight) in capsules containing also Vit. B complex, and, in the active arms, Q10 ubiquinol. Capsules can be opened and the content drunk or chewed, if children have difficulties with swallowing capsules.

Also known as: tocopherols

ASD Active compound; ASD Placebo; PMS Active compound; PMS Placebo

Multi-Vitamin B complex DIETARY_SUPPLEMENT

Multi-Vitamin B complex including Vit. B1, B2, B3, B5, B6, B8, B9, and B12, in capsules containing also Vit. E and, in the active arms, Q10 ubiquinol. Capsules can be opened and the content drunk or chewed, if children have difficulties with swallowing capsules.

ASD Active compound; ASD Placebo; PMS Active compound; PMS Placebo

Eligibility Criteria

• Age: 2 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Both parents or a legally authorized patient representative (LAR) must provide written informed consent. The parents and guardian must be able to understand and comply with the experimental protocol;
• Subjects of both sexes, aged between 2 and 40 years old, may be included in the study;
• The subject must meet DSM-5 criteria for a primary diagnosis of Autism Spectrum Disorder (idiopathic autism) or carry a documented deletion of human chromosome 22q13.33 or mutation in the SHANK3 gene (Phelan-McDermid Syndrome);
• Subjects with idiopathic autism must pass the threshold score for Autism of the Autism Diagnostic Observation Schedule;
• Baseline Children's Global Assessment Scale score must be between 45 and 59;
• Patients treated with psychoactive drugs (neuroleptics, antiepileptics, etc.) are enrolled only if the treatment and dosage of these drugs has been constant for at least 3 months prior to enrollment in the trial and is kept constant throughout the 8-month duration of the trial;
• Patients undergoing any kind of behavioral intervention must have must have started the intervention at least 3 months prior to enrollment and the intervention must remain unchanged throughout the 8-month duration of the trial;
• The patient is able to swallow the capsule or his/her parents are available to open it and administer immediately its content in a small quantity of juice or soft-drink.

You may not qualify if:

• Patients who meet any of the following criteria will not be recruited in the study:
• Patients with autism secondary to known genetic syndromes other than Phelan-McDermid syndrome (for example, Rett syndrome, fragile-X syndrome, etc.);
• Presence of brain malformations or major structural anomalies visible by magnetic resonance imaging;
• Patients with autism secondary to epileptic encephalopathy or with idiopathic autism comorbid with seizures more frequent than one episode every 6 months despite ongoing antiepileptic drug therapy;
• Patients with autism accompanied by marked facial dysmorphism and/or congenital malformations;
• Patients treated with anticoagulants;
• Patients with serious medical illnesses (chronic renal disease, severe liver disease, cardiovascular disorders, uncontrolled hypertension with systolic pressure values\> 170 and diastolic pressure\> 100 mm Hg, malignant tumors, HIV infection);
• Patients with a history of acute cerebrovascular episodes;
• Patients with a history of stomach bleeding or active peptic ulcer;
• Patients with documented allergy, hypersensitivity or intolerance to one of the excipients of the experimental or comparative product.
• Trial interruption criteria:
• Patients whose medical conditions require starting treatment with anticoagulants.
• Patients with severe medical conditions starting during the 8-month duration of the trial.
• Patients who undergo a change in psychopharmacological or behavioral treatment during the 8-month duration of the trial.

Sponsors & Collaborators

• Antonio Persico: lead
• Associazione Italiana Sindrome di Phelan-McDermid (AISPHEM): collaborator
• University of Bari: collaborator

Study Sites (1)

Interdipartimental Program "Autismo 0-90" at "G. Martino" Universitary Hospital

Messina, ME, I-98125, Italy

Location

Related Publications (17)

• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. In: Association AP, editor. Fifth Edition ed: American Psychiatric Publishing, Arlington; 2013.

  BACKGROUND

• Persico AM, Arango C, Buitelaar JK, Correll CU, Glennon JC, Hoekstra PJ, Moreno C, Vitiello B, Vorstman J, Zuddas A; European Child and Adolescent Clinical Psychopharmacology Network. Unmet needs in paediatric psychopharmacology: Present scenario and future perspectives. Eur Neuropsychopharmacol. 2015 Oct;25(10):1513-31. doi: 10.1016/j.euroneuro.2015.06.009. Epub 2015 Jun 20.

  PMID: 26166453 BACKGROUND

• Kalayci M, Unal MM, Gul S, Acikgoz S, Kandemir N, Hanci V, Edebali N, Acikgoz B. Effect of coenzyme Q10 on ischemia and neuronal damage in an experimental traumatic brain-injury model in rats. BMC Neurosci. 2011 Jul 29;12:75. doi: 10.1186/1471-2202-12-75.

  PMID: 21801363 BACKGROUND

• Kumari S, Mehta SL, Milledge GZ, Huang X, Li H, Li PA. Ubisol-Q10 Prevents Glutamate-Induced Cell Death by Blocking Mitochondrial Fragmentation and Permeability Transition Pore Opening. Int J Biol Sci. 2016 Apr 27;12(6):688-700. doi: 10.7150/ijbs.13589. eCollection 2016.

  PMID: 27194946 BACKGROUND

• Duberley KE, Heales SJ, Abramov AY, Chalasani A, Land JM, Rahman S, Hargreaves IP. Effect of Coenzyme Q10 supplementation on mitochondrial electron transport chain activity and mitochondrial oxidative stress in Coenzyme Q10 deficient human neuronal cells. Int J Biochem Cell Biol. 2014 May;50:60-3. doi: 10.1016/j.biocel.2014.02.003. Epub 2014 Feb 15.

  PMID: 24534273 BACKGROUND

• Rossignol DA, Frye RE. Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Front Physiol. 2014 Apr 22;5:150. doi: 10.3389/fphys.2014.00150. eCollection 2014.

  PMID: 24795645 BACKGROUND

• Frustaci A, Neri M, Cesario A, Adams JB, Domenici E, Dalla Bernardina B, Bonassi S. Oxidative stress-related biomarkers in autism: systematic review and meta-analyses. Free Radic Biol Med. 2012 May 15;52(10):2128-41. doi: 10.1016/j.freeradbiomed.2012.03.011. Epub 2012 Apr 18.

  PMID: 22542447 BACKGROUND

• Adams JB, Baral M, Geis E, Mitchell J, Ingram J, Hensley A, Zappia I, Newmark S, Gehn E, Rubin RA, Mitchell K, Bradstreet J, El-Dahr JM. The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels. J Toxicol. 2009;2009:532640. doi: 10.1155/2009/532640. Epub 2009 Aug 26.

  PMID: 20107587 BACKGROUND

• Ghezzo A, Visconti P, Abruzzo PM, Bolotta A, Ferreri C, Gobbi G, Malisardi G, Manfredini S, Marini M, Nanetti L, Pipitone E, Raffaelli F, Resca F, Vignini A, Mazzanti L. Oxidative Stress and Erythrocyte Membrane Alterations in Children with Autism: Correlation with Clinical Features. PLoS One. 2013 Jun 19;8(6):e66418. doi: 10.1371/journal.pone.0066418. Print 2013.

  PMID: 23840462 BACKGROUND

• Adams JB, Holloway C. Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med. 2004 Dec;10(6):1033-9. doi: 10.1089/acm.2004.10.1033.

  PMID: 15673999 BACKGROUND

• Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, Gehn E, Loresto M, Mitchell J, Atwood S, Barnhouse S, Lee W. Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatr. 2011 Dec 12;11:111. doi: 10.1186/1471-2431-11-111.

  PMID: 22151477 BACKGROUND

• Adams JB, George F, Audhya T. Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements. J Altern Complement Med. 2006 Jan-Feb;12(1):59-63. doi: 10.1089/acm.2006.12.59.

  PMID: 16494569 BACKGROUND

• Palmieri L, Persico AM. Mitochondrial dysfunction in autism spectrum disorders: cause or effect? Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):1130-7. doi: 10.1016/j.bbabio.2010.04.018. Epub 2010 May 9.

  PMID: 20441769 BACKGROUND

• Gvozdjakova A, Kucharska J, Ostatnikova D, Babinska K, Nakladal D, Crane FL. Ubiquinol improves symptoms in children with autism. Oxid Med Cell Longev. 2014;2014:798957. doi: 10.1155/2014/798957. Epub 2014 Feb 23.

  PMID: 24707344 BACKGROUND

• Mousavinejad E, Ghaffari MA, Riahi F, Hajmohammadi M, Tiznobeyk Z, Mousavinejad M. Coenzyme Q10 supplementation reduces oxidative stress and decreases antioxidant enzyme activity in children with autism spectrum disorders. Psychiatry Res. 2018 Jul;265:62-69. doi: 10.1016/j.psychres.2018.03.061. Epub 2018 Apr 4.

  PMID: 29684771 BACKGROUND

• Adams JB, Audhya T, Geis E, Gehn E, Fimbres V, Pollard EL, Mitchell J, Ingram J, Hellmers R, Laake D, Matthews JS, Li K, Naviaux JC, Naviaux RK, Adams RL, Coleman DM, Quig DW. Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder-A Randomized, Controlled 12-Month Trial. Nutrients. 2018 Mar 17;10(3):369. doi: 10.3390/nu10030369.

  PMID: 29562612 BACKGROUND

• Harony-Nicolas H, De Rubeis S, Kolevzon A, Buxbaum JD. Phelan McDermid Syndrome: From Genetic Discoveries to Animal Models and Treatment. J Child Neurol. 2015 Dec;30(14):1861-70. doi: 10.1177/0883073815600872. Epub 2015 Sep 8.

  PMID: 26350728 BACKGROUND

MeSH Terms

Conditions

Autism Spectrum Disorder; Telomeric 22q13 Monosomy Syndrome; Autistic Disorder; Neurobehavioral Manifestations

Interventions

Vitamin E; Tocopherols

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Antonio M. Persico, MD

  University of Messina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, all care providers, investigators and outcome assessors are blind to treatment status, as well as patients and family. Three investigators with no contact with patients and families provide the appropriate blisters to patients. One investigator not involved in outcome assessment interacts with families for any question regarding the trial or medical issues, screening outcome assessors from contacts by families in between assessments (0-4-8 months). Families are requested to refrain from commenting their experience and trial outcome on social media.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Full Professor in Child & Adolescent Neuropsychiatry

Model Details: Each patient receives active compound \[Q10 ubiquinol + Vit. E and polyvitamin B\] for 4 months and placebo \[Vit. E and B\] for another 4 months. The total duration of the trial is 8 months. Half of the patients receive the active compound during months 1-4 and placebo during months 5-8, while the remaining half receives placebo during months 1-4 and active compound during months 5-8. Patients are assessed at T0, T4 and T8 mo. Administration of active compound and placebo is in double-blind.

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 18, 2020
• Study Start: March 9, 2019
• Primary Completion: December 31, 2022
• Study Completion: August 31, 2023
• Last Updated: March 18, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)