Slowing Down Disease Progression in Premanifest SCA: a Piloting Interventional Exergame Trial (SlowSCA)

This is a piloting study using continuous motor training provided via whole body-controlled video games (exergames) to establish proof-of-concept evidence that such training leads to motor and neural changes in pre-manifest subjects with spinocerebellar ataxias (SCA).

Study Overview

• Status: Unknown
• Conditions: Spinocerebellar Ataxia
• Intervention / Treatment: Other: Motor training

Detailed Description

In many neurodegenerative diseases, including spinocerebellar ataxias (SCA), large populations of neurons are already lost and compensatory resources exhausted at time of clinical diagnosis. This calls for early intervention strategies aiming to slow down disease progression already at the premanifest stage of the disease. Here we propose the world-first interventional study aiming to delay onset in a rare genetic neurodegenerative disease. Specifically, we propose a piloting study using continuous motor training provided via whole body-controlled video games (exergames) to establish proof-of-concept evidence that such training leads to motor and neural changes in pre-manifest SCA subjects. The subclinical effects will be unravelled within an intraindividual control study design by elaborated quantitative Video Management System (VICON®)-based movement analysis and structural and functional 3 Tesla (T) magnetic resonance imaging. This will provide unique insights in underlying motor and neural networks and compensatory strategies. If successful, this piloting trial will provide the basis for a rigorous international multi-center large-scale study in a larger SCA population. Moreover, it will stimulate complementary tandem projects on effects of motor training on neural functioning and molecular pathways in premanifest SCA mouse models.

• Study Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Tuebingen, Baden-Württemberg, Germany, 72076
      • Recruiting
      • University Hospital
      • Contact: Matthis Synofzik, PD Dr.; Phone Number: +49-7071-2982060; Email: matthis.synofzik@uni-tuebingen.de
      • Contact: Winfried Ilg, Dr.; Phone Number: +49-7071-2989125; Email: winfried.ilg@uni-tuebingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult persons (age 18-80 years) who (i) are a blood-related relative of an index subject with a known SCA 1,2,3 or 6 mutation and who (ii) have a score value of <8 points on the Scale for the Assessment and Rating of Ataxia (SARA)
• full capacity to consent to study participation after extensive information (fully Informed Consent)

Exclusion Criteria:

• Cognitive deficits which prevent full comprehension of the study requirements and/or training requirements
• Comorbid diseases that place severe constraints on a continous training with whole-body controlled exergames (e.g. severe visual or hearing deficits; severe paresis; severe movement disorders other than ataxia)
• Comorbid neurologic disease other than ataxia (e.g. prior stroke or brain trauma)
• Pregnant or breast-feeding persons
• Lack of capacity for full informed consent according to established psychiatric criteria for full informed consent

Magnetic Resonance Imaging (MRI) exclusion criteria:

• cardiac pacemakers
• artificial heart valves
• metal prostheses
• implanted magnetic metal parts (screws, plates and similar devices)
• intrauterine devices (for instance, for contraceptive purposes)
• shrapnel parts and other metal pieces
• non-removable braces and metal dentures
• non-removable acupuncture needles
• insulin pumps and infusion ports
• tattoos, eye shadow and other metal-containing make-up
• The subject has decreased sensitivity to temperature and / or decreased tolerance towards elevated body temperatures or warming of body parts.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Motor training; The motor training comprise of demanding coordinative exercises based on commercially available developed by Microsoft Game Console (XBOX Kinect™) exergames that specifically target ataxia dysfunctions.	Other: Motor training; The motor training will comprise of demanding coordinative exercises based on commercially available developed by Microsoft Game Console (XBOX Kinect™) exergames that specifically target ataxia dysfunctions.; Other Names: Exergaming

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait score	Decrease in a quantitative composite gait score consisting of body sway and gait variability in walking challenge conditions (mattress), assessed by VICON-based motion tracking	Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain networks captured	Changes in brain networks captured by specific neuroimaging focussing on brain grey matter volume (VBM), brain fibre tracking (DTI) and functional connectivity of the cerebellum with other brain regions (resting-state connectivity)	Day 43
Quantitative movement parameters	Set of quantitative movement parameters for complex whole-body movements (gait, stand, fast sequences of goal-directed stepping movements) (VICON-based motion tracking).	Day 43
Ataxia severity	Clinical ataxia severity according to the Scale for the Assessment and Rating of Ataxia (SARA)	Day 43
Daily activity	Objectively measured level of daily activity in subjects' real-world settings (body-worn motions sensors; ActivePal®)	Day 43
Brain-derived neurotrophic factor	Increase of serum brain-derived neurotrophic factor (BDNF)	Day 43

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): February 1, 2017
• Study Completion (Anticipated): May 1, 2017

Study Registration Dates

• First Submitted: August 11, 2016
• First Submitted That Met QC Criteria: August 11, 2016
• First Posted (Estimate): August 16, 2016

Study Record Updates

• Last Update Posted (Estimate): August 16, 2016
• Last Update Submitted That Met QC Criteria: August 11, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Training; Neurodegenerative diseases; Rare disease; Exergaming; Spinocerebellar ataxia; Motor exercises; Premanifest stage
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Disease Attributes; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Cerebellar Diseases; Cerebellar Ataxia; Disease Progression; Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations
• Other Study ID Numbers: SlowSCA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO