Defining Outcome Measures for Behavioural and Emotional Problems in Dystrophinopathies (D-BRAIN)

Study aims to develop and to evaluate the neurophysiological and physiological response to a classical conditioning task.To better understand how Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) impacts mental health and how to assess it. Participants invited to complete questionnaires about behaviour, cognitive function and social interactions, complete computer tasks and have an optional MRI brain scan,

Study Overview

• Status: Recruiting
• Conditions: DMD; BMD

Detailed Description

The investigation aims to develop and to evaluate the neurophysiological and physiological response to a classical conditioning task, which is comparable to findings that have been made in the mdx dystrophic mouse (deficient in Dp427). The investigators will assess correlations between the specific DMD/BMD genotype and susceptibility to conditioning, as well as the relationship between conditioning and behavioural/emotional characteristics of the syndrome. At the end of the study, the objective is to deliver a comprehensive test battery that is suitable for use in a trial of AON delivery to improve brain function.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Anna Kolesnik, Dr; Phone Number: 44 (0) 20 7905 2600; Email: braindmd@ucl.ac.uk
• Study Contact Backup: Name: Natasha Aslam, MSc; Phone Number: 44 (0) 20 7905 2600; Email: natasha.aslam@ucl.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

40 DMD, 30 BMD patients and 30 age-matched controls.

Description

Inclusion Criteria:

• DMD patients:

  1. Male
  2. Age range 7-17 years
  3. A genetically proven diagnosis of DMD.
  4. A genetic mutation that abrogates expression of Dp427 alone (assigned in DMD Group 1: Dp427-/Dp140+) or both Dp427 and Dp140 (assigned to DMD Group 2: Dp427-/Dp140-).
  5. Ability to consent/assent

BMD patients:

1. Male
2. Age range 7-17 years
3. A genetically proven diagnosis of BMD.
4. A genetic mutation that decreases expression of Dp427 alone (assigned to BMD Group 1), of both Dp427 and Dp140 (assigned to BMD Group 2).
5. Ability to consent/assent

Control participants:

1. Male
2. Age range 7-17 years.
3. Ability to consent/assent

Exclusion Criteria:

• DMD & BMD patients:

  1. Significant visual or hearing impairment
  2. Specific phobias or sensory sensitivities to stimuli similar to the ones used in this study
  3. Current participation in a clinical trial investigating a new drug involved in dystrophin modulation.
  4. Inability to consent (for parents/guardians or self-reporting participants aged 16 and 17) or assent. This will exclude the rare individuals with extremely severe learning disability, as the assent in these patients is impossible (or the consent in self-reporting participants aged 16 and 17).

Control participants:

1. Significant visual or hearing impairment
2. Specific phobias or sensory sensitivities to stimuli similar to the ones used in this study
3. Any diagnosis of neurological or psychiatric condition

General exclusion criteria for MRI:

1. Claustrophobia
2. Pacemakers and defibrillators
3. Nerve stimulators
4. Intracranial clips
5. Intraorbital or intraocular metallic fragments
6. Cochlear implants
7. Ferromagnetic implants (e.g. thoracic implant for scoliosis)
8. Inability to lie supine during less than 45 minutes
9. Not having a general practitioner
10. Severe learning disability which will require a general anaesthetic

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group differences between DMD, BMD and controls in the initial aversive unconditioned stimulus.	Following an emotional response task, an interim analysis will be done after the first 30 patients have been tested (10 DMD, 10 BMD, 10 controls). A favourable outcome will demonstrate a difference in the emotional response of these groups. Groups will complete questionnaires, an emotional response task, and a fine motor assessment.	through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To observe any difference between and within BMD, DMD and control groups in regard to learning, habituation and extinction	This will be measured by analysis measuring any difference between and within groups (10 BMD, 10 DMD and 10 control). Physiological responses generated by the task will be measured, along with neural imaging.	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: University College, London

Publications and helpful links

Helpful Links

• Duchenne clinical trial listing
• Health Research Authority research summary

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2022
• Primary Completion (Estimated): November 19, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: August 8, 2024
• First Submitted That Met QC Criteria: August 29, 2024
• First Posted (Actual): September 3, 2024

Study Record Updates

• Last Update Posted (Actual): September 3, 2024
• Last Update Submitted That Met QC Criteria: August 29, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Antisense oligonucleotide
• Other Study ID Numbers: 21/WM/0267

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The results of the study will be published in peer-reviewed scientific journal(s), presented at relevant national and international meetings, and reported as part of submissions to regulatory and funding bodies (Joint Research & Development Office, GOSH & ICH; NHS Research Ethics Committee; GOSH Charity). Participants will be asked if they wish to be contacted when the results are published, and if in agreement they will be informed by letter/email of any resulting publications.

Drug and device information, study documents

• 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