Exploring Bulbar Function, Speech And Communication Development in SMA Type 1

NCT05954455 | Recruiting

• 1 other identifier: 19NM18
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

5q-spinal muscular atrophy (5q-SMA) is a rare, autosomal recessive neuromuscular disease characterized by degeneration of motor neurons in the spinal cord and lower brainstem with progressive muscle atrophy, weakness, and paralysis. The incidence is 1 in 7-10,000 live births. 5q-SMA presents a wide range of phenotypes that are classified into five clinical groups depending on age of onset and maximum motor milestone achieved. SMA type 1 presents shortly after birth and before six months of age with inability to achieve independent sitting and limited life expectancy due to respiratory complications (high mortality rate by 2 years of age). In addition to the severe gross-motor and respiratory impairment, bulbar weakness and dysfunction represent an obstacle to the development of verbal skills in these patients. To date, very little is known about these functions in children with SMA 1. With the increasing number of long-term SMA 1 survivors worldwide thanks to the availability of new pharmacological treatments, it has become obvious that treated children show new phenotypes, presenting changes not only in motor and respiratory function, but also in other domains, including bulbar function, speech and communication development. We aim to investigate the evolution of bulbar function and speech/communication development in children with SMA type 1 treated with approved disease-modifying therapies through validate scales and questionnaires for the paediatric population. Additional neurophysiological and neuroimaging studies will be offered on an optional basis to further investigate the underlying brain electrical activity, and brain structural and functional organization. The information gathered would promote the definition of additional outcome measures capturing improvement at these levels. A better understanding of the development of these areas would help to plan SMA 1- tailored supportive programs provided by speech and language therapists, thus enhancing the current recommendations for management in SMA.

Conditions

SMA1

Outcome Measures

Primary Outcomes (16)

• Bulbar function - Changes from baseline

  Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score( Worse) - Max score 6 (Better performance)

  Baseline, Visit Month 12, Month 24, and Months 36

• Bulbar function

  Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score 1( Worse) - Max score 6 (Better performance)

  Visit Month 6

• Bulbar function

  Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score 1 (Worse) - Max score 6 (Better performance)

  Visit Month 18

• Bulbar function

  Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score 1( Worse) - Max score 6 (Better performance)

  Visit Month 30

• Speech and Communication - Changes from baseline

  MacArthur-Bates Communicative Development Inventory (MCDI) - Words and Gestures or Words and Sentences For 8-18 month-olds looking at words and gestures, the following min score (worse performance) - max scores (better performance) exist: Phrases understood: 0/28 Vocabulary understood: 0/396 Vocabulary used: 0/396 Early gestures: 0/18 Later gestures: 0/45 Total gestures: 0/63 For 18-30 month-olds looking at words and sentences, the following min score (worse performance) - max scores (better performance) exist: Words produced = 0/680 Irregular words = 0/25 Overregularized words = 0/45 Sentence complexity = 0/37

  Baseline, Month 12, Month 24, and Months 36

• Speech and Communication

  MacArthur-Bates Communicative Development Inventory (MCDI) - Words and Gestures or Words and Sentences For 8-18 month-olds looking at words and gestures, the following min score (worse performance) - max scores (better performance) exist: Phrases understood: 0/28 Vocabulary understood: 0/396 Vocabulary used: 0/396 Early gestures: 0/18 Later gestures: 0/45 Total gestures: 0/63 For 18-30 month-olds looking at words and sentences, the following min score (worse performance) - max scores (better performance) exist: Words produced = 0/680 Irregular words = 0/25 Overregularized words = 0/45 Sentence complexity = 0/373

  Visit Month 6

• Speech and Communication

  MacArthur-Bates Communicative Development Inventory (MCDI) - Words and Gestures or Words and Sentences For 8-18 month-olds looking at words and gestures, the following min score (worse performance) - max scores (better performance) exist: Phrases understood: 0/28 Vocabulary understood: 0/396 Vocabulary used: 0/396 Early gestures: 0/18 Later gestures: 0/45 Total gestures: 0/63 For 18-30 month-olds looking at words and sentences, the following min score (worse performance) - max scores (better performance) exist: Words produced = 0/680 Irregular words = 0/25 Overregularized words = 0/45 Sentence complexity = 0/37

  Visit Month 18

• Speech and Communication

  MacArthur-Bates Communicative Development Inventory (MCDI) - Words and Gestures or Words and Sentences For 8-18 month-olds looking at words and gestures, the following min score (worse performance) - max scores (better performance) exist: Phrases understood: 0/28 Vocabulary understood: 0/396 Vocabulary used: 0/396 Early gestures: 0/18 Later gestures: 0/45 Total gestures: 0/63 For 18-30 month-olds looking at words and sentences, the following min score (worse performance) - max scores (better performance) exist: Words produced = 0/680 Irregular words = 0/25 Overregularized words = 0/45 Sentence complexity = 0/37

  Visit Month 30

• Speech and Communication - Changes from baseline

  Peabody Picture Vocabulary Test (PPVT)

  Baseline, Visit Month 6, Month 12, Month 18, Month 24, Month 30 and Months 36

• Speech and Communication

  Peabody Picture Vocabulary Test (PPVT) Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.

  Visit Month 6

• Speech and Communication

  Peabody Picture Vocabulary Test (PPVT) Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.

  Visit Month 18

• Speech and Communication

  Peabody Picture Vocabulary Test (PPVT) Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.

  Visit Month 30

• Speech and Communication - Changes from Baseline

  Social Communication Questionnaire (SCQ) Minimum value is 0, maximum value is 39, higher score means worse outcome (The threshold varies depending on countries and researchers).

  Baseline, Month 12, Month 24, and Months 36

• Speech and Communication

  Social Communication Questionnaire (SCQ) Minimum value is 0, maximum value is 39, higher score means worse outcome (The threshold varies depending on countries and researchers).

  Visit Month 6

• Speech and Communication

  Social Communication Questionnaire (SCQ) Minimum value is 0, maximum value is 39, higher score means worse outcome (The threshold varies depending on countries and researchers).

  Visit Month 18

• Speech and Communication

  Social Communication Questionnaire (SCQ) Minimum value is 0, maximum value is 39, higher score means worse outcome (The threshold varies depending on countries and researchers).

  Visit Month 30

Secondary Outcomes (4)

• Cognitive function - Changes from baseline

  Baseline, Month 12, Month 24, and Months 36

• Cognitive function

  Visit Month 6

• Cognitive function

  Visit Month 18

• Cognitive function

  Visit Month 30

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

In the first instance, we will recruit SMA 1 paediatric patients (up to 18 years of age) who are under the care of the Neuromuscular team at the Dubowitz Neuromuscular Centre, London, UK, and who are being treated with any approved disease-modifying therapies. A total number of 30 patients is expected to be enrolled in the pilot phase of the study.

You may qualify if:

• genetic documentation of 5q SMA;
• onset of clinical signs and symptoms at ≤ 6 months (180 days) of age;
• years of age
• treatment with any of the approved disease-modifying therapies;
• parent(s)/legal guardian(s) willing and able to complete the informed consent process and comply with study procedures and visit schedule.

You may not qualify if:

• any clinically significant medical finding that - in the judgment of the Investigator - will make the patient unsuitable for participation in, and/or unable to complete the study procedures;
• parent(s)/legal guardian(s) unable or unwilling to comply with study procedures and/or refuses to sign consent form.
• any clinically significant medical finding that - in the judgment of the Investigator - will make the patient unsuitable for participation in, and/or unable to complete the study procedures;
• parent(s)/legal guardian(s) unable or unwilling to comply with study procedures and/or refuses to sign consent form.

Sponsors & Collaborators

• Institute of Child Health: lead
• Great Ormond Street Hospital for Children NHS Foundation Trust: collaborator

Study Sites (1)

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

RECRUITING

Central Study Contacts

Giovanni Baranello, MD

CONTACT

02079052872; g.baranello@ucl.ac.uk

Marta Zancolli, PhD

CONTACT

02079052188; m.zancolli@ucl.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: July 20, 2023
• Study Start: March 21, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 16, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)