ISRCTN ISRCTN40092306
DOI https://doi.org/10.1186/ISRCTN40092306
IRAS number 328273
Secondary identifying numbers CPMS 57586, IRAS 328273
Submission date
31/10/2023
Registration date
02/11/2023
Last edited
13/08/2024
Recruitment status
No longer recruiting
Overall study status
Ongoing
Condition category
Nervous System Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Friedreich’s ataxia (FA) is an inherited genetic condition. FA affects the part of the brain that controls movement and balance (the cerebellum). It also affects the nerves which carry signals from the brain to the rest of the body. People with FA experience symptoms that get worse over time. These include movement and balance difficulties, speech and swallowing issues, and muscle weakness. Other symptoms can include diabetes mellitus and heart problems. Many people with FA live with significant physical disability and reduced life expectancy. Currently, there is no cure for FA, and more research on this rare condition is needed. Performing clinical trials in rare conditions like FA is challenging. Current clinical rating scales and many outcome measures are subjective. The results may differ depending on who performs the assessment. Often, assessments are not sensitive enough to detect changes over a short time frame. Instrumented assessments of gait and balance, may be useful as alternative outcome measures. They are already used to assess gait and balance issues (ataxia) in some conditions. They are less subjective than current measures and may be better at detecting changes. This study will investigate instrumented assessments of gait and balance in FA. This will be in a specialist gait laboratory and via wearable sensors. It will investigate if these assessments show a consistent pattern. It will also check if these assessments are sensitive enough to measure changes in FA over a year compared to current outcome measures.

Who can participate?
People aged 14 to 65 years, years and above with a confirmed diagnosis of FA

What does the study involve?
Participants will attend the study centre in Newcastle upon Tyne for three visits over 12 months. These will take place at baseline (the start), month 6 and month 12.

Visit assessments will include clinical assessments including physical examination and review of medical history, standard clinical rating tools for FA and tests of upper limb coordination. Participants will also complete questionnaires about ataxia, quality of life and fatigue. Assessments of balance and gait will be performed in a gait laboratory and using wearable sensors. Following each visit, participants will continue wearing a wearable sensor for seven days at home.

Data collected in this study will be combined for analyses with data collected via a separate protocol (under separate approvals and governance) undertaken at the Hertie Institute for Clinical Brain Research and Centre for Integrative Neuroscience, in Germany (Tübingen).

What are the possible benefits and risks of participating?
There will be no direct benefits to individual participants. The study will provide data on the severity and progression of FA. It will investigate new methods for measuring ataxia in FA and will inform the design of future research.

The study involves tests of balance and walking and there may be a risk of falling or becoming tired. The assessments are delivered in an area designed for this type of activity. All staff are trained and experienced in delivering these assessments. Opportunities for regular breaks will be provided.

Study questionnaires include questions on quality of life and well-being. These questions may be distressing for some participants. Participants can contact study staff at any point if they are worried or have difficulty with a questionnaire.

Where is the study run from?
Newcastle University (UK)

When is the study starting and how long is it expected to run for?
June 2023 to August 2026

Who is funding the study?
The French Friedreich’s Ataxia Association (AFAF) (France)

Who is the main contact?
Dr Yi Shiau Ng, yi.ng@newcastle.ac.uk

Contact information

Dr Yi Shiau Ng
Scientific, Principal Investigator

Wellcome Centre for Mitochondrial Research
Newcastle University
4th Floor, Cookson Building
Framlington Place
Newcastle upon Tyne
NE2 4HH
United Kingdom

ORCiD logoORCID ID 0000-0002-7591-2034
Phone +44 (0)191 208 3084
Email yi.ng@newcastle.ac.uk

Study information

Study designObservational single UK centre longitudinal study (12-month follow-up per participant)
Primary study designObservational
Secondary study designLongitudinal study
Study setting(s)Home, Internet/virtual, Laboratory, Medical and other records
Study typeOther
Participant information sheet 44521_PIS_Adult_V3.0_17Oct23.pdf
Scientific titleA longitudinal laboratory and real-world study of gait and balance in people with Friedreich ataxia
Study objectivesGait and balance problems have been identified by people with ataxias as the main symptoms that they would like to be addressed in clinical trials.

A number of clinical rating scales are commonly used in both clinical practice and research to determine the severity of ataxia. However, there are a number of limitations in using such measures including their semi-quantitative and subjective nature, inter-rater variability (differences depending on who performs the assessment), and lack of sensitivity to detect change over shorter time periods (e.g., 6-12 months), with ceiling effects.
Also, the small effect size of studies using clinical rating scales as the primary outcome means a large sample size is required, which is a significant barrier to the delivery of clinical trials, especially in rare conditions such as Friedreich’s Ataxia.

The availability of robust clinical outcome measures that are reliable and sensitive to change is therefore essential for future clinical research in this condition.

Recent work has shown that instrumented measures of gait have the potential to be feasible and reliable outcome measures for people with ataxias.

This study aims to:
1. Identify outcome measures that can reliably detect disease progression in Friedreich’s Ataxia over a short period ( one year )
2. Validate instrumented measures of gait (including in a specialist gait laboratory and via wearable sensors) against traditional clinical rating scales for Friedreich’s Ataxia.
Ethics approval(s)

Approved 30/08/2023, East of England - Cambridge South Research Ethics Committee (Equinox House, City Link, Nottingham, NG2 4LA, United Kingdom; +44 (0)207 104 8171; cambridgesouth.rec@hra.nhs.uk), ref: 23/EE/0173

Health condition(s) or problem(s) studiedFriedreich ataxia
InterventionThis study is a collaboration between the Wellcome Centre for Mitochondrial Research, Newcastle, UK, and the Hertie Institute for Clinical Brain Research and Centre for Integrative Neuroscience, Tubingen Germany. Data collected at both centres (under separate protocols and separate regulatory permissions) will be combined as part of the analyses. This registration relates to the UK study and data collection only.

Participants in the study will be assessed at study visits at Baseline, Month 6, and Month 12. Study visit assessments will consist of:
- Collection of medical history and results from previous clinical assessments
- Clinical rating scales of Friedreich’s Ataxia, ataxia and cognition
- Functional assessments of upper limb coordination and gait
- Instrumented assessment of gait in a gait laboratory
- Participant completed questionnaires (Participant Reported Outcomes) of balance, ataxia, quality of life and fatigue (collected remotely via an online system)

Study visits will last approximately four hours each.

Following each visit, participants will undergo habitual activity monitoring (via wearable sensor) in a free-living environment (at home) for seven days.

Following completion of the Month 12 visit assessments (at the end of the seven-day activity monitoring period) study participation will be complete.
Intervention typeMixed
Primary outcome measureBalance and gait measured using stabilometry (force plate analysis), an instrumented walkway (GaitRite) and wearable sensors (Ax6 and Opal) at baseline, month 6 and month 12
Secondary outcome measures1. Investigate how balance and gait outcomes are influenced by wearable sensor location and configuration (i.e. single sensor vs. 3 Opal sensors) measured using gait data generated in a specialist gait laboratory and in the real world at baseline, month 6 and month 12
2. Validate gait outcomes measured using the wearable sensors against gait outcomes measured via the instrumented walkway at baseline, month 6 and month 12
3. Compare data collected in the real world via wearable sensor with data from clinical rating scales, questionnaires and gait laboratory assessments at baseline, month 6 and month 12
Overall study start date21/06/2023
Completion date31/08/2026

Eligibility

Participant type(s)Patient
Age groupMixed
Lower age limit14 Years
Upper age limit65 Years
SexBoth
Target number of participants16
Key inclusion criteria1. Genetically confirmed Friedreich’s Ataxia
2. Aged 14 to 65 years
3. Able to stand and walk unaided for at least 20 m
4. Able to provide informed consent
5. Able to follow instructions and comply with the study protocol
6. Willing to wear a small sensor on the lower back for seven consecutive days
7. No other known neurological or musculoskeletal disorder affecting balance and mobility
Key exclusion criteria1. Lacking the capacity to provide informed consent
2. Enrolled in interfering therapy or clinical drug trial currently or within last 3 months
3. Pregnancy at the time of enrolment
4. Any other reason, which in the opinion of the recruiting investigator would preclude involvement in the study
Date of first enrolment01/11/2023
Date of final enrolment31/08/2025

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

NIHR Newcastle Clinical Ageing Research Unit (CARU)
Freeman Hospital
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Sponsor information

Funders

Funder type

Research organisation

l'Association Française de l'Ataxie de Friedreich (AFAF)

No information available

Results and Publications

Intention to publish date31/08/2027
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
Publication and dissemination planThe results from the study will be published via scientific papers in peer reviewed publications and via presentations and posters at conferences and patient/public information days and events. The study may also be publicised on a number of partner and charity websites and results disseminated in a variety of print and online media. Social media platforms may also be used to communicate research developments and to stimulate interest and communication amongst patient groups, academics and the public.

De-identified study data may also be shared with, or uploaded to, a data repository.

Study participants will be advised that their individual study results will not be made available however they will be provided with a summary of the study results once available.
IPD sharing planThe data-sharing plans for the current study have not yet been finalised and will be made available at a later date.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Participant information sheet Adult
version 3.0
17/10/2023 02/11/2023 No Yes
Participant information sheet Older children
version 3.0
17/10/2023 02/11/2023 No Yes
Participant information sheet Parent
version 3.0
17/10/2023 02/11/2023 No Yes
Protocol file version 3.0 17/10/2023 02/11/2023 No No

Additional files

44521_PROTOCOL_V3.0_17Oct23.pdf
44521_PIS_OlderChildren_V3.0_17Oct23.pdf
Older children
44521_PIS_Parent_V3.0_17Oct23.pdf
Parent
44521_PIS_Adult_V3.0_17Oct23.pdf
Adult

Editorial Notes

13/08/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 31/08/2024 to 31/08/2025.
2. The overall study end date was changed from 31/08/2025 to 31/08/2026.
3. The intention to publish date was changed from 31/08/2026 to 31/08/2027.
4. Contact details updated.
02/11/2023: Study's existence confirmed by the HRA.