Effects of a Supervised Rehabilitation Program on Disease Severity in Spastic Ataxias

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay Clinical Trial

Official title:

IMPACT, a Supervised Rehabilitation Program for Spastic Ataxias: A Rater-blinded, Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06261424
• Other study ID #: 2024-1426
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2024
• Est. completion date: March 2027

Study information

• Verified date: May 2024
• Source: Université du Québec à Chicoutimi
• Contact: Elise Duchesne, Ph D.
• Phone: 418-590-3552
• Email: educhesn[@]uqac.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Spastic ataxias are a group of diseases causing symptoms such as walking difficulties and balance impairments that lead to a high risk of falls. No pharmacological treatments exist to treat these diseases. Unfortunately, little effort is made to develop non-pharmacological treatments specific to spastic ataxias despite the detrimental impact of the disease on several aspects of an individual's life and the high cost of falls for society each year. The three objectives of this project are: 1) to determine the effect of a 12-week rehabilitation program on disease severity as compared with usual care for individuals with spastic ataxias; 2) to identify which factors can help (or not) the implementation of the program in the clinical settings ("reel world"); and 3) to explore the cost-benefits of IMPACT [rehabIlitation prograM for sPAstiC aTaxias]. The team has developed the program to specifically target symptoms present in these patients and was previously pilot-tested. Based on the results obtained in this pilot project, positive effects are expected concerning the disease severity of participants. The investigators want, with this project, provide to health care professionals an option to offer better-suited services to people living with spastic ataxia worldwide.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: March 2027
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• have a confirmed genetic diagnosis of ARSACS or SPG7
• be able to maintain standing position and to transfert
• be authorized by their treating neurologist
• speak French or English
• be able to give informed consent.

Exclusion Criteria:

• have active participation in a rehabilitation program (self-reported information)
• have another condition causing physical limitations
• be uncomfortable in a swimming pool
• be pregnant.

Related Conditions & MeSH terms

• Ataxia
• Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay
• Cerebellar Ataxia
• Intellectual Disability
• Muscle Spasticity
• Optic Atrophy
• Paraplegia
• Spinocerebellar Ataxias

Intervention

Procedure:
• IMPACT - rehabIlitation prograM for sPAstiC aTaxias
The rehabilitation program will last 12 weeks and consists of three training sessions of 60 minutes per week (2 sessions in a therapy room and 1 session in an adapted pool with multiple levels of water) for a total of 36 sessions. Participants will be divided into 7 subgroups of 6 participants and each sub-group will be supervised by one physiotherapist (PT) and one physiotherapy technologist for safety considerations. It will focus on these three domains: 1) postural control; balance, trunk-limbs and multi-joints control and coordination and 3) functional mobility. Each domain contains a standardized list of exercises with different difficulty levels and specific times allocation. All exercises will be executed by the participants at each session at the appropriate difficulty level. The initial level of difficulty for each exercise will be determined by the PT based on individual results of the pre-intervention assessment and on individual performance, fatigue level and safety.

Locations

Country	Name	City	State
Canada	CIUSSS de la Capitale-Nationale, Hôpital de Baie-Saint-Paul	Baie-Saint-Paul	Quebec
Canada	CIUSSS de la Capitale-Nationale, Hôpital de La Malbaie	La Malbaie	Quebec
Canada	CIUSSS du Centre-Sud-de-l'Île-de-Montréal, installation Centre de réadaptation Lucie-Bruneau	Montréal	Quebec
Canada	CIUSSS de la Capitale-Nationale, installation IRDPQ	Québec	Quebec
Canada	Clinique des maladies neuromusculaires du Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay-Lac-Saint-Jean, installation Hôpital Jonquière	Saguenay	Quebec

Sponsors (12)

Lead Sponsor

Collaborator

Université du Québec à Chicoutimi

Cégep de Jonquière, Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-St-Jean, Corporation de recherche et d'action sur les maladies héréditaires (CORAMH), Integrated University Health and Social Services Center of the Capitale-Nationale, Laval University, McGill University, Muscular Dystrophy Canada, Université de Sherbrooke, Université du Québec a Montréal, University of Alberta, University of Calgary

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Lessard I, Masterman V, Cote I, Gagnon C, Duchesne E. A rehabilitation program to increase balance and mobility in ataxia of Charlevoix-Saguenay: An exploratory study. PLoS One. 2022 Dec 28;17(12):e0279406. doi: 10.1371/journal.pone.0279406. eCollection 2022. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Severity of ataxia	The severity of ataxia assessed using the Scale for the assessment and rating of Ataxia (SARA) has been chosen as the main variable based on several considerations. 1) it is one of the most widely used scales among recessive cerebellar ataxias in intervention studies, 2) it includes lower limbs motor impairments-induced mobility limitations items, 3) is significantly correlated with key impairments variables such as standing balance and walking speed, 4) and is a candidate for outcome measurement in foreseeable clinical trials.; It has eight categories with accumulative score ranging from 0 (no ataxia) to 40 (most severe ataxia) It showed evidence of adequate content validity and excellent construct validity and internal consistency in ARSACS and we recently validated the French version.	64 weeks
Secondary	Medication change	Patients will be asked about the possibility of changing their medication. A list of medications will also be provided by the pharmacy.	64 weeks
Secondary	Weight	Patients weight in kilograms	64 weeks
Secondary	height	Patients height in meters	64 weeks
Secondary	Physical activities	The Rapid Assessment of Physical Activity (RAPA) is a questionnaire used to assess physical activity levels.; Each question has a 'Yes' or 'No' option. The total score of the first seven items is out of 7; participants choose which question corresponds to their activity level. Any score less than 6 is considered suboptimal. Strength training and flexibility are scored separately (strength training = 1, flexibility = 2, both = 3)	64 weeks
Secondary	Walking speed.	The 10-meter walk test will be used to assess the short-distance walking speed at comfortable and maximum speeds. The validity and reliability of the 10mWT are both excellent in ARSACS (ICC = 0.99).	64 weeks
Secondary	Standing balance	Berg balance scale will be used to assess balance and risk of falling. Its validity has been demonstrated in ARSACS.18 Participants' level of confidence in their balance will be assessed using the simplified balance confidence scale specific to daily activities; It has 14 (0-4) categories with accumulative score ranging from 0 to 56. Interpretation: 0-20, wheelchair bound; 21-40, walking with assistance; 41-56, independent.	64 weeks
Secondary	Balance confidence	Activities specific balance confidence-simplified (ABC-S) scale will aslo be use to assess balance (0-3 likert scale) This questionnaire includes 15 evaluation items, rated from 0 (not at all confident) to 3 (very confident), according to the person's confidence in maintaining their balance when performing various activities. The total score ranges from 0 (minimum confidence) to 45 (maximum confidence), and is obtained by adding together the scores for each item and converting them into a percentage.	64 weeks
Secondary	Sitting balance	Sitting balance and trunk control will be assessed with the Ottawa sitting scale (OSS).; The first six items are tested with the participant's feet on the ground ( /24) and the next six with the feet off the ground ( /24). The total score is calculated by adding together the scores for the two subsections (maximum score out of /48).	64 weeks
Secondary	Activities of Daily Living	The Barthel Index will assess the level of independence in performing daily living activities.	64 weeks
Secondary	Muscle tone	Lower limb muscle tone (spasticity) will be measured with the modified Ashworth scale.; Score each muscle group evaluated according to the table below. *Scoring is performed within the available range of motion. 0: No increase in muscle tone. 1: Discrete increase in muscle tone manifested by a twitch followed by release or by minimal resistance at the end of the movement. 1+: Discrete increase in muscle tone manifested by a twitch followed by minimal resistance perceived over less than half the joint amplitude. 2: More marked increase in muscle tone affecting most of the joint amplitude, the joint being easily mobilized. 3: Significant increase in muscle tone making passive mobilization difficult. 4: Affected joint is fixed (no passive movement possible).	64 weeks
Secondary	Life habits	The Assessment of Life Habits Questionnaire 4.0. (LIFE-H) was used to assess participation. It includes a total of 96 activities with one total score, two subscores (daily activities and social activities) and 12 domains divided equally between both subscores. For each activity, the level of accomplishment, type of assistance required and level of satisfaction are rated. Accomplishment includes the difficulty level and assistance required: a mean score of "0" refers to a complete disruption of participation (i.e. activity not accomplished), and "10" refers to full participation (i.e. activity accomplished without difficulty and assistance). The satisfaction level is measured on a 4-point scale, where a higher score indicates higher satisfaction ("4"). For the 3.0 version, a change of 0.5 (/9) is considered a minimal clinically important difference but is not documented for the version 4.0.	64 weeks
Secondary	Community mobility	The daily rest-activity pattern will be assessed using an ActiGraph wGT3X-BT activity monitor worn on the nondominant arm for 7 consecutive days before and after the intervention period. Intradaily variability and interdaily stability (IS), M10 (most active 10-hours), L5 (least active 5-hours), and relative amplitude (RA) will be derived using nonparametric rhythm analysis. The patient's perception of mobility limitations will be measured by the Life Space Assessment questionnaire.	7 consecutives days, 2 times
Secondary	Plasma	3 x 10ml EDTA tubes will be collected to obtain 6 x 0.5ml cryovials of plasma (protein)	64 weeks
Secondary	DNA	3 x 10ml EDTA tubes will be collected to obtain 3 x 2ml cryovials of Buffy Coat (DNA).	64 weeks
Secondary	Serum	3 x 5ml SST serum tubes will be collected to obtain 12 x 0.5ml serum (protein) cryovials.	64 weeks
Secondary	RNA	3 PAXgene 2.5ml tubes (RNA) will be collected and frozen as is.	64 weeks
Secondary	Urine	10 ml of urine will be collected and separated into 12 cryovials of 0.5 ml.	64 weeks
Secondary	Saliva	12 ml of saliva will be collected to obtain 12 cryovials of 0.5 ml.	64 weeks
Secondary	Mobility Life-space	Life-Space Assessment (LSA-F) is a 20-items questionnaire measures the extent of mobility, taking into account the person's interactions with the environment. It assesses mobility habits in five living environments: the rooms of the home (or living unit for people living in sheltered housing), the surroundings of the home (or living unit/housing environment), the neighborhood, the city and outside the city.; Mobility area - Composite score, which is obtained by combining the level of mobility area achieved, the frequency of travel in each mobility area and the assistance required (technical aid and/or assistance of a person) to get there. The score ranges from 0 to 120, where 120 corresponds to an unrestricted mobility area.	64 weeks
Secondary	Ataxia impact scale	Person-reported ataxia impact scale (PRAIS) is self-administered questionnaire consists of 38 questions and aims to understand the impact of ataxia on daily life. A score out of 100 results.	64 weeks
Secondary	Lower limb coordination	It will be measured using the Lower Extremity Motor Coordination Test. It is a reliable tool in ARSACS (ICC = 0.82-0.99).	64 weeks
Secondary	Peak respiratory flow and cough	Peak expiratory flow (PEF) is the maximum speed at which air can be expelled from the lungs during forced expiration.	64 weeks
Secondary	Fatigue	Fatigue will be assess with the Fatigue Severity Scale (FSS) This scale is a method of assessing the impact of fatigue on the subject. It is a short questionnaire that assesses the level of fatigue. The questionnaire contains nine statements that assess the severity of fatigue symptoms on a 7-level likert scale and produce a score between 9 and 63. A high score is a sign of fatigue	64 weeks
Secondary	Falls.	The fall history with and without injury will be self-reported according to the recommendations of the group of Elley et al. Participants will have to complete every day a fall logbook and a research assistant will contact them each month to document the circumstances and consequences of falls including injuries and medical consultations.	64 weeks
Secondary	Patient-reported impression of change.	The patients-global impression of change will be used (3 questions, 7-level Likert self-reported scale) to assess the impression of change.It is sensitive to change. This questionnaire gives the patient's perception. The higher the score, the worse the situation.	64 weeks
Secondary	Anxiety and Depression	Hospital Anxiety and Depression scale will assess anxiety and Depression; The HADS is a screening instrument for anxiety and depressive disorders. It comprises 14 items rated from 0 to 3. Seven questions relate to anxiety (total A) and seven to depression (total D), giving two scores (maximum score for each = 21).	64 weeks
Secondary	Pain characteristics	Brief Pain Inventory Short Form	64 weeks
Secondary	Functional lower extremity strength	The 30CST is a measurement that assesses functional lower extremity strength. The total number of correctly performed sit-to-stand repetitions is counted. If the participant is more than halfway upright when the 30 seconds have elapsed, count this as a repetition. If the participant is unable or unwilling to perform the test correctly, enter "0 repetitions" for each trial on the scoring sheet. The validity of the result of each test must be entered on the scoring sheet (valid or invalid).	64 weeks
Secondary	Focus group with intervention group participants	Each participant will take part in one focus group after the rehabilitation program. Also, a semi-structured interview guide covering the 7 dimensions of the TFA will be used.	1 day
Secondary	Focus groups with stakeholders	One focus group per site will be conducted before and after the intervention. In addition, during the rehabilitation program, each PT will be asked to fill out a journal of observations every week that includes the CFIR intervention items. In addition, the Determinant of Implementation Behavior. Questionnaire will be administered to PT and assistants at T0 and T3.	12 weeks
Secondary	Lower limb muscle activation	It will be measured using surface EMG. Surface myoelectric signals will be recorded at 2000 HZ using a 16-channel wireless system (Trigno™ EMG, Delsys, MA, USA).	64 weeks
Secondary	Quality of life	Quality of life will be assessed with SF-12 is a generic questionnaire that assesses health-related quality of life from the participant's point of view. It can be self-administered or completed during an interview. It comprises 12 assessment items, divided into 7 domains. The scoring system provides two quality-of-life scores (0 to 100: poor to excellent), i.e., a subtotal for mental and social quality of life (MCS) and a subtotal for physical quality of life (PCS).	64 weeks
Secondary	CBA analyses and Willingness to pay	Estimating the costs related to the use of health services, falls with and without injuries, and improvement in quality of life and our health indicators (main and secondary outcomes). Using data collected in medical records and the hospitalization data, we will use different variables to take into account the use of health services such as: 1) visits physicians or health care professionals; 2) home visits by home-care professionals; and 3) emergency or hospital stays. We will also use the project's information relative to the cost of the rehabilitation program such as: 1) the number of hours of assessments and supervision of the program/type of professional and 2) the hourly rate of professionals. The cost of setting up a rehabilitation program will be estimated by combining human and material resources.	64 weeks
Secondary	Gait's temporal parameters	The GAITRite system is a 14ft carpet containing sensors activated by pressure exerted by the feet and providing x and y coordinates. Then, the footprint analysis can provides the gait temporal parameters such as step time, step length, cadence and speed.	64 weeks
Secondary	Stance balance	Force platform	64 weeks
Secondary	Postural balance	Postural balance will be assess with the wobble chair. This test measures the postural balance of the trunk during a balance task in a seated position on an unstable chair, where only movements of the lumbar spine are allowed to restore balance.	64 weeks