Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04193228 |
| Other study ID # |
pending |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 2, 2021 |
| Est. completion date |
November 27, 2023 |
Study information
| Verified date |
November 2023 |
| Source |
University College London Hospitals |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Distal Hereditary Motor Neuropathy (dHMN) is a rare inherited neuromuscular disorder. It is
characterised by distal weakness. The condition usually manifests in the second decade of
life and progresses slowly. Though patients usually have a normal lifespan it is a disabling
condition and most eventually need aids to walk. In order to improve walking quality in
patient with dHMN, research is needed to understand the impairments that lead to altered gait
patterns, and to develop interventions to correct walking gait conservatively.
In this proposed trial our goal is to explore the relationships between muscle structure,
function and gait patterns for people with Distal Hereditary Motor Neuropathy. Over 12
months, muscle changes in dHMN are going to be observed in terms of structure and function
using MRI, myometry and 3D motion analysis. In addition, the effect of a 16 weeks exercises
program on muscle structure and function in dHMN is going to be measured by the same
observational methods. To address walking gait directly in dHMN, gait patterns with and
without wearing carbon fibre ankle foot orthoses (AFO)will be measured using 3D motion
analysis.
Description:
Objectives: The primary objective (objective 1) is to:
1. explore the natural history of muscle structure and function in Distal Hereditary Motor
Neuropathy (dHMN) over one year.
The secondary objectives are:
2. to ascertain relationships between intramuscular fat fraction (measured by MRI), muscle
volume, isokinetic muscle strength (measured by dynamometry) and moments/power
generation (measured by 3D gait analysis) (objective 2).
3. to explore the effect of bilateral carbon fibre ankle foot orthoses (AFO) on the
kinetics and kinematics of gait of people with DHMN (measured by 3D gait analysis)
(objective 3).
4. to explore the effect of resistance training of the ankle muscles in people with ankle
muscle strength over grade 4 MRC scale on muscle structure, function, and gait patterns
(objective 4).
Type of trial: A prospective cohort study in adult patients with dHMN with a single UK site.
Trial design and methods: This study (participants with dHMN and control participants) is
proposed to take place over 3 years in one site in the UK (NHNN). Participants with dHMN aged
over 18 for potential enrolment in the study will be identified through existing inherited
neuropathy cohort clinics at NHNN and healthy control participants will be invited. If they
show interest in participating, they will be given the relevant Patient Information Sheets
and Informed Consent Forms.
Objective 1&2: dHMN participants will undergo the following measures: MRI scans of the legs,
isokinetic strength and power measures of the lower limb using the HUMAC Norm dynamometer,3D
motion analysis to capture kinetic and kinematic data of complete gait cycles. Clinical
assessments will be undertaken to measure: gait speed and endurance, joint range of motion,
foot posture, pain and sensory impairment. For direct comparison of gait deviations, twenty
age and gender matched health controls will also be recruited to undergo the same measures.
Scans, dynamometry and clinical measures will be repeated after one year to explore the
natural history of the disease.
Objective 3: The dHMN participants recruited for objective 1 will undergo additional gait
analysis: wearing just shoes (control condition), wearing their own prescribed orthoses
(where appropriate), and wearing bilateral carbon fibre AFOs. The order of wearing or not
wearing the AFOs will be randomised to account for learning and/or fatigue effects.
Objective 4: The participants from objective 1 will be invited to participate in the strength
training study and will be screened to see if they meet the inclusion criteria. The primary
criteria will be that at least one of the major muscle groups of the ankle, dorsiflexors or
plantarflexors, will score over 4/5 on the MRC scale. There might be a need for recruiting
more participants if less than 10 from objective 1 participants met the inclusion criteria.
Up to 15 participants will be prescribed a home based, resistance training trial for 16
weeks, supervised by the PhD candidate through weekly phone calls and monthly monitoring
through an app, and progression visits. Response to training will be analysed by: MRI scans,
myometry, and 3D motion analysis.
Trial duration per participant: 16 months Estimated total trial duration: 36 months Planned
trial sites: The National Hospital for Neurology and Neurosurgery (NHNN), UCLH NHS Foundation
Trust.
Total number of participants planned: 20 participants with dHMN and 20 matching control
participants will be recruited for objective 1. Participates with dHMN will be invited to
participate for objective 2 and 3.
Main inclusion/exclusion criteria: The main disease to be investigated is dHMN. The key
inclusion criteria are: adult patients aged 18 or above with clinically proven dHMN; patients
who are able to complete calf and thigh myometry, able to walk for 10 minutes without walking
aids, and have no contraindication to MRI scanning. For objective 4, at least one of the
major muscle groups of the ankle, dorsiflexors or plantarflexors, will score over 4/5 on the
MRC scale. The key exclusion criteria are: patients having undergone lower limbs surgery in
the year prior to the trial enrolment or planned to have lower limb surgery in the 16 months
of the study; bilateral arthrodesis; participants having another medical condition which
precludes them having an MRI scan; patients with a known diagnosis of another neurological
disease. Control participants must have no known neuromuscular disease, have no
contraindication to MRI scanning, be able to complete calf and thigh myometry and 3D gait
analysis.
