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Q10 Ubiquinol in Autism Spectrum Disorder and in Phelan-McDermid Syndrome. (Q10ASD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04312152
Recruitment Status : Enrolling by invitation
First Posted : March 18, 2020
Last Update Posted : March 18, 2020
Sponsor:
Collaborators:
Associazione Italiana Sindrome di Phelan-McDermid (AISPHEM)
University of Bari
Information provided by (Responsible Party):
Antonio Persico, University of Messina

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.

Condition or disease Intervention/treatment Phase
Autism Spectrum Disorder Phelan-McDermid Syndrome Dietary Supplement: Q10 Ubiquinol Dietary Supplement: Vitamin E Dietary Supplement: Multi-Vitamin B complex Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Randomized, Placebo-controlled, Cross-over, Double-blind Study of a Metabolic Support Therapy With Q10 Ubiquinol and a Multivitamin B and E Complex in Two Cohorts of Patients With Idiopathic and Syndromic Autism (Phelan-McDermid Syndrome)
Actual Study Start Date : March 9, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : August 31, 2023


Arm Intervention/treatment
Active Comparator: PMS Placebo

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
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.
Other Name: tocopherols

Dietary Supplement: Multi-Vitamin B complex
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.

Active Comparator: ASD Placebo

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
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.
Other Name: tocopherols

Dietary Supplement: Multi-Vitamin B complex
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.

Experimental: PMS Active compound

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
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.

Dietary Supplement: Vitamin E
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.
Other Name: tocopherols

Dietary Supplement: Multi-Vitamin B complex
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.

Experimental: ASD Active compound

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
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.

Dietary Supplement: Vitamin E
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.
Other Name: tocopherols

Dietary Supplement: Multi-Vitamin B complex
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.




Primary Outcome Measures :
  1. Change in Vineland Adaptive Behavior Scales scores [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    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.

  2. Change in Childhood Autism Rating Scale score [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    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.

  3. Change in Clinical Global Impression of Improvement scale scores between experimental and active comparator arms. [ Time Frame: 4 and 8 months (record once at the end of each arm) ]
    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. Change in Visual Analog Scales scores [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    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.


Secondary Outcome Measures :
  1. Children's Global Assessment Scale [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    The Children's Global Assessment Scale provides a global measure of level of functioning in children and adolescents. The measure provides a single rating on a 0-100 scale, with higher scores indicating better functioning.

  2. Social Responsiveness Scale [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    65-item questionnaire used to assess social impairment, communication deficits and repetitive behaviors in children and adolescents 4-18 years old. Autism is severe, moderate, or mild when T-scores are above 75, 66-75, or 60-65, respectively. Scores below 60 are not clinically significant.

  3. Repetitive Behaviors Scale - Revised [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    44-item questionnaire used to assess repetitive behaviors. Filled by parents for children 6-17 years old. Behaviors are rated on a 0-3 scale to measure increasing symptom severity, as does the overall global score ranging 0-100.

  4. Aberrant Behavior Checklist [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    58-item questionnaire used to assess problem behaviors with parents or guardians. Behaviors are rated on a 0-3 scale to measure increasing symptom severity.

  5. Short Sensory Profile [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    38-item questionnaire filled by caregivers to assess the sensory profile of patients, including sensory processing, modulation, and behavioral/emotional responses. The overall score ranges from 0 to 190, with lower scores reflecting greater symptom severity.

  6. Conners' Parent Rating Scale-Revised [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    48-item rating scale used to evaluate through parental reports the presence and intensity of childhood hyperactivity/inattention, impulsivity and externalizing behaviors. Each item is rated on a 0-3 scale to reflect increasing symptom severity.

  7. Child Behavior Checklist [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    The Child Behavior Checklist/6-18 provides ratings for 20 competence and 120 behavioral problem items of youth aged 6-18 years old by parental report. Each item is scored 0-2, to reflect symptom severity or frequency. Standard scores are scaled so that 50 is average for the youth's age and gender, with a standard deviation of 10 points.

  8. Intellectual Quotient [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    Intellectual quotient measured as a standardized score with population mean 100 and standard deviation 15, using one cognitive test per subject, chosen depending on age and language development (either Griffiths Developmental Rating Scales, Wechsler Intelligence Scale for Children - Fourth Edition, or Leiter III).

  9. The Quality of Life in Autism Questionnaire [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    A questionnaire used to assess parental quality of life either broadly (part A, 28 items, score range 28-140) or specifically related to the autism present in their offspring (part B, 20 items, score range 20-100). Total score range 48-240, with higher scores indicating better quality of life.

  10. The World Health Organization's Quality of Life Questionnaire [ Time Frame: At 0, 4 and 8 months (pre- and post-treatment after each arm) ]
    A questionnaire used to assess parental quality of life in four domains: physical, psychological, social, and environmental. The score can range from 15 to 105, with a higher score being indicative of a higher quality of life.

  11. Measurement of protein carbonylation level as a marker of oxidative stress in leukocytes. [ Time Frame: Blood drawn at 0, 4 and 8 months (pre-and post-treatment after each arm). ]
    Blood drawing, isolation of leukocytes by Ficoll gradient and measurement of protein carbonylation by oxyblot.

  12. Measurement of the activity of mitochondrial respiratory chain complexes. [ Time Frame: Blood drawn at 0, 4 and 8 months (pre-and post-treatment after each arm). ]
    Blood drawing, isolation of leukocytes by Ficoll gradient and measurement of the activity of mitochondrial respiratory chain complexes normalized by citrate synthase activity.

  13. Measurement of expression levels of mitochondrial respiratory chain complexes. [ Time Frame: Blood drawn at 0, 4 and 8 months (pre-and post-treatment after each arm). ]
    Blood drawing, isolation of leukocytes by Ficoll gradient and measurement of the expression levels of mitochondrial respiratory chain complexes by Western-Blotting.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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;
  2. Subjects of both sexes, aged between 2 and 40 years old, may be included in the study;
  3. 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);
  4. Subjects with idiopathic autism must pass the threshold score for Autism of the Autism Diagnostic Observation Schedule;
  5. Baseline Children's Global Assessment Scale score must be between 45 and 59;
  6. 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;
  7. 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;
  8. 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.

Exclusion Criteria:

Patients who meet any of the following criteria will not be recruited in the study:

  1. Patients with autism secondary to known genetic syndromes other than Phelan-McDermid syndrome (for example, Rett syndrome, fragile-X syndrome, etc.);
  2. Presence of brain malformations or major structural anomalies visible by magnetic resonance imaging;
  3. 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;
  4. Patients with autism accompanied by marked facial dysmorphism and/or congenital malformations;
  5. Patients treated with anticoagulants;
  6. 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);
  7. Patients with a history of acute cerebrovascular episodes;
  8. Patients with a history of stomach bleeding or active peptic ulcer;
  9. Patients with documented allergy, hypersensitivity or intolerance to one of the excipients of the experimental or comparative product.

Trial interruption criteria:

  1. Patients whose medical conditions require starting treatment with anticoagulants.
  2. Patients with severe medical conditions starting during the 8-month duration of the trial.
  3. Patients who undergo a change in psychopharmacological or behavioral treatment during the 8-month duration of the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04312152


Locations
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Italy
Interdipartimental Program "Autismo 0-90" at "G. Martino" Universitary Hospital
Messina, ME, Italy, I-98125
Sponsors and Collaborators
Antonio Persico
Associazione Italiana Sindrome di Phelan-McDermid (AISPHEM)
University of Bari
Investigators
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Principal Investigator: Antonio M. Persico, MD University of Messina
Publications:
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. In: Association AP, editor. Fifth Edition ed: American Psychiatric Publishing, Arlington; 2013.

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Responsible Party: Antonio Persico, Full Professor in Child & Adolescent Neuropsychiatry, University of Messina
ClinicalTrials.gov Identifier: NCT04312152    
Other Study ID Numbers: Q10_study_ASD
First Posted: March 18, 2020    Key Record Dates
Last Update Posted: March 18, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Antonio Persico, University of Messina:
Ubiquinol-10
Coenzyme Q10
Autism
Mitochondria
Oxidative stress
Cognitive symptoms
Chromosome 22q13 3 deletion syndrome
Additional relevant MeSH terms:
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Chromosome Disorders
Syndrome
Chromosome Deletion
Autistic Disorder
Autism Spectrum Disorder
Disease
Pathologic Processes
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Monosomy
Aneuploidy
Chromosome Aberrations
Congenital Abnormalities
Genetic Diseases, Inborn
Vitamins
Vitamin E
Tocopherols
Folic Acid
Vitamin B Complex
Micronutrients
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Hematinics