Intranasal Ketamine With Dexmedetomidine for the Treatment of Children With Autism Spectrum Disorder

• ClinicalTrials.gov Identifier: NCT03434366
• Recruitment Status: Recruiting
• First Posted: February 15, 2018
• Last Update Posted: May 26, 2020
• Sponsor: Guangzhou Women and Children's Medical Center
• Information provided by (Responsible Party): Ying Jun She, MD, Guangzhou Women and Children's Medical Center

Study Description

Brief Summary:

Autism spectrum disorder (ASD) is a life-long neurodevelopmental disorder characterized by qualitative abnormalities in reciprocal social interactions and patterns of communication, and by a restricted, stereotyped, repetitive repertoire of interests and activities. The use of medications in adolescents and young adults with ASD is extremely common. However, few data address the effectiveness and harms of medications specifically in this population.

The purpose of the study is to determine the efficacy and safety of intranasal ketamine with dexmedetomidine in children with ASD.

Condition or disease	Intervention/treatment	Phase
Autism Spectrum Disorder	Drug: ketamine and dexmedetomidine; Drug: ketamine; Drug: Saline	Phase 2

Detailed Description:

The use of medications in adolescents and young adults with ASD is extremely common. few data address the effectiveness and harms of medications specifically in this population. A previous study reported the first case study demonstrating clinical improvement in mood and eye fixation scores from intranasal ketamine treatment in a "complicated" subject with autism spectrum disorderHowever,The purpose of the study is to determine the efficacy and safety of intranasal ketamine with dexmedetomidine in children with ASD.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Intranasal Ketamine With Dexmedetomidine for the Treatment of Children With Autism Spectrum Disorder
• Actual Study Start Date: January 20, 2018
• Estimated Primary Completion Date: December 30, 2023
• Estimated Study Completion Date: December 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: ketamine and dexmedetomidine group; intranasal ketamine and dexmedetomidine was treated in the children	Drug: ketamine and dexmedetomidine; intranasal ketamine and dexmedetomidine for treatment for autism spectrum disorder; Other Name: intranasal ketamine and dexmedetomidine
Experimental: ketamine group; intranasal ketamine was treated in the children	Drug: ketamine; intranasal ketamine for treatment for autism spectrum disorder; Other Name: intranasal ketamine
Placebo Comparator: control group; intranasal insaline was used in the children	Drug: Saline; intranasal saline for treatment for autism spectrum disorder; Other Name: intranasal saline

Outcome Measures

Primary Outcome Measures :

1. Autism Diagnostic Interview Revised (ADI-R) [ Time Frame: change from baseline at 2, 5 and 12 weeks ]
   The Autism Diagnostic Interview Revised is an investigator-based semi-structured diagnostic interview, The ADI-R provides empirically derived diagnostic algorithms for three subdomains of qualitative impairments. The social interaction domain includes questions about emotional sharing, offering and seeking comfort, social smiling, and social responding comprising four subscores. The second domain (communication) assesses stereotyped expressions, pronoun reversal, and the social usage of language (B1-B4). In the third domain repetitive and stereotyped behavior as hand- and finger mannerisms, unusual sensory interest or activities are investigated by four subscales. Most items are scored from zero to three, relying on the interviewer to make judgements on child's behaviour based on the recall of information from parents/carers. . A total score is then calculated for each of the three subdomains. The ADI-R has an algorithm for autism based on scores in these three areas and on onset.
2. Autism Diagnostic Observation Schedule (ADOS) [ Time Frame: change from baseline at 2, 5 and 12 weeks ]
   The Autism Diagnostic Observation Schedule (ADOS) is a semi-structured assessment of communication, social interaction and play or imaginative use of materials for individuals suspected of having autism or other ASD. It consists of four modules, each of which is appropriate for children, adolescents and adults of differing developmental and language levels, ranging from no expressive or receptive language to verbally fluent adults. The examiner selects the module that is most appropriate for a particular child, adolescent on the basis of his/her expressive language level and chronological age. Selected algorithm items relating to social interaction and communication are then entered into an algorithm. The scores must meet the separate cut-offs for both the communication and social domains and the cut-off for the summation of the two. Repetitive behaviours are recorded and coded as part of the clinical observations but do not contribute to the ADOS summary algorithm.

Secondary Outcome Measures :

1. autism behavior checklist (ABC) [ Time Frame: change from baseline at 2, 5 and 12 weeks ]
   ABC is a scale used for nonadaptive behaviors created to screen and indicate the probability of a diagnosis of autism. The questionnaire approaches 57 atypical behaviors related to five areas: sensorial, relational, use of body and objects, and social skills. Scales> 67 was diagnosised ASD, compare the change in scales in different time point(from baseline to endpoint)
2. magnetic resonance spectroscopy(MRS) [ Time Frame: change from baseline at 5 and 12 weeks ]
   compare the metabolite concentrations and ratios in brain from Baseline to Endpoint (NAA,Glu,Gln,Cho,Cr,mI)
3. Childhood Autism Rating Scale (CARS) [ Time Frame: change from baseline at 2, 5 and 12 weeks ]
   CARS assesses the child on a scale from 1 to 4 in each of 15 dimensions or symptoms (including the ability to relate to people, emotional response, imitation, body use, object use, listening response, fear or nervousness, verbal communication, nonverbal communication, activity level, level and reliability of intellectual response, adaptation to changes, visual response, taste, smell and touch responses and general impressions). A total score of at least 30 strongly suggests the presence of autism. Children who score between 30 and 36 have mild-to-moderate autism while those with scores between 37 and 60 have severe autism. Change in CARS from Baseline to Endpoint.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 15 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. meet autism diagnostic criteria based on DSM-5/ADI-R/ADOS
2. children aged 2 years through 15 years of age
3. parents/guardians can cooperate with the study and sign informed consent
4. ASA score I or II

Exclusion Criteria:

1. with epilepsy or other genetic diseases
2. changes in drugs or in any intervention during the study
3. Presence of cardiac disease including coronary artery disease, congestive heart failure, or uncontrolled hypertension per medical history
4. Airway instability, tracheal surgery, or tracheal stenosis per medical history.
5. History of drug or alcohol abuse
6. Central nervous system masses or hydrocephalus per medical history

Contacts and Locations

Contacts

Contact: YJ She, Dr.; 862038076243; yjsheh@yeah.net

Locations

China, Guangdong

Guangzhou Women and Children Medical Center; Recruiting

Guangzhou, Guangdong, China, 510000

Contact: Ying-Jun She, Doctor 862038076243 yjsheh@yeah.net

Sponsors and Collaborators

Guangzhou Women and Children's Medical Center

Investigators

• Principal Investigator: Qing Zhao, Doctor; Guangzhou Women and Children's Medical Center

More Information

• Responsible Party: Ying Jun She, MD, Department of Anesthesiology, Guangzhou Women and Children's Medical Center
• ClinicalTrials.gov Identifier: NCT03434366
• Other Study ID Numbers: intranasal ketamine
• First Posted: February 15, 2018
• Last Update Posted: May 26, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ying Jun She, MD, Guangzhou Women and Children's Medical Center:

Autism Spectrum Disorder; ketamine; dexmedetomidine

Additional relevant MeSH terms:

Disease; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Pathologic Processes; Neurodevelopmental Disorders; Mental Disorders; Dexmedetomidine; Ketamine; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents