Gait and Balance Impairment in Rare and Very Rare Neurological Diseases

Healthy Clinical Trial

— GALVANISE  

Official title:

Gait and Balance Impairment in Rare and Very Rare Neurological Diseases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06343558
• Other study ID #: 24C302
• Status: Recruiting
• Start date: May 30, 2023
• Est. completion date: May 1, 2027

Study information

• Verified date: March 2024
• Source: Istituto Auxologico Italiano
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Rare and very rare neurological diseases primarily or exclusively affect the nervous system with a prevalence of < 5 out of 10'000 and 100'000 people, respectively. Besides these, there are undiagnosed neurological diseases: neurological conditions without a diagnosis after completing a full diagnostic examination. Rare, very rare, and undiagnosed neurological diseases are complicated and progressive and often cause variegated motor signs, impairments, and syndromes. Balance and gait are frequently affected in these conditions, already at the clinical examination. These balance and gait impairments limit activities and cause an increased risk of falling. Falls can eventually result in injuries, even severe. There are only a few studies about these diseases, likely because of their rarity. Hence, the clinical presentation and the course of rare and very rare diseases are poorly known or even unknown. Essential information for these conditions' diagnosis, prognosis, treatment and rehabilitation is missing. MaNeNeND is an observational study underway at the Fondazione IRCCS Istituto Neurologico "Carlo Besta" (Milano) aimed at detailing the clinical and biological features of very rare and undiagnosed neurological diseases. Research questions: 1. Do patients with rare (Ra), very rare (V) and undiagnosed (U) neurological diseases suffer a balance and gait impairment? 2. Is there a correlation between the clinical and instrumental severity of the balance and gait impairment in RaVU neurological diseases? 3. Are instrumental measures more sensitive in detecting balance and gait impairments in patients affected by a RaVU neurological disease than the clinical measures? 4. Do the balance and gait impairments in RaVU neurological diseases worsen in time? The current project aims at diagnosing, quantifying and detailing the balance and gait impairment in rare, very rare and undiagnosed neurological diseases. To this aim, questionnaires, clinical scales and instrumental tests will be administered to these patients to collect a wide range of balance and gait measures. These measures will also integrate those collected with MaNeNeND to provide a more detailed description of patients with rare, very rare and diagnosed neurological diseases. Participants will complete two questionnaires: the Dizziness Handicap Inventory - short form (DHI-sf, an ordinal score of self-perceived balance) and the Modified Fatigue Impact Scale (MFIS, an ordinal score of self-perceived fatigue). Moreover, a clinician will administer the Mini Balance Evaluation Systems Test (Mini-BESTest, an ordinal score of balance), the 10 m walking test (for measuring the gait speed and other gait parameters) and the Timed Up and Go test (an instrumental measure of mobility and balance). Walking and the Timed Up and Go tests will be recorded with a trunk-worn inertial measurement unit. Finally, participants will be asked to complete an instrumental upright stance and gait assessment, the first consisting of standing on posturographic plates and the second of walking on a treadmill equipped with force sensors. When walking on the treadmill, an optoelectronic system will also record the position in time of limbs and trunk. The quantification of the severity of the balance and gait impairment of the patients suffering a rare, very rare or undiagnosed neurological disease will highlight these persons' therapeutic and rehabilitative needs. Comparing the balance and gait impairment of rare, very rare and undiagnosed diseases with those of multiple sclerosis, Parkinson's disease and peripheral neuropathy will highlight if the formers' balance and gait impairment has unique characteristics that could help ease the diagnosis of these uncommon conditions. The longitudinal measurements on rare, very rare and undiagnosed diseases will be paramount to identifying prognostic factors. In addition, the data collected in the current study will be crucial for future studies, for example, for estimating the sample size in clinical trials.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: May 1, 2027
• Est. primary completion date: May 1, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion criteria

• Multiple sclerosis, Parkinson's disease, peripheral neuropathy of the lower limbs or rare or ultrarare neurological disease (e.g. la Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome - CANVAS, ORPHAcode: 504476; Wilson's disease, ORPHAcode: 905)
• undiagnosed neurological disease, i.e. a neurological disease that remains unknown after a full diagnostic assessment;
• age > 18 years;
• ability to stand upright with no assistance and no assistive device for > 30 seconds;
• ability to walk without assistance and with no assistive device for > 50 m;
• ability to give their informed consent. Exclusion criteria
• pregnancy or breastfeeding
• any other medical conditions affecting by itself balance and gait (e.g. lower limb amputation, hemiparesis due to a stroke)
• major orthopaedic surgery (e.g. hip or knee replacement).

Related Conditions & MeSH terms

• Healthy
• Healthy Aging
• Multiple Sclerosis
• Nervous System Diseases
• Parkinson Disease
• Peripheral Nervous System Diseases
• Peripheral Neuropathy
• Rare Diseases

Intervention

Other:
• Questionnaires, clinical scales and instrumental tests
Questionnaires, clinical scales and instrumental tests to collect a wide range of balance and gait measures.

Locations

Country	Name	City	State
Italy	IRCCS Istituto Auxologico Italiano	Milano	Milan
Italy	IRCCS Istituto Neurologico Carlo Besta	Milano

Sponsors (2)

Lead Sponsor	Collaborator
Istituto Auxologico Italiano	IRCCS Istituto Neurologico Carlo Besta

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Caronni A, Gervasoni E, Ferrarin M, Anastasi D, Brichetto G, Confalonieri P, Di Giovanni R, Prosperini L, Tacchino A, Solaro C, Rovaris M, Cattaneo D, Carpinella I. Local Dynamic Stability of Gait in People With Early Multiple Sclerosis and No-to-Mild Neurological Impairment. IEEE Trans Neural Syst Rehabil Eng. 2020 Jun;28(6):1389-1396. doi: 10.1109/TNSRE.2020.2991636. Epub 2020 Apr 30. — View Citation

Caronni A, Sterpi I, Antoniotti P, Aristidou E, Nicolaci F, Picardi M, Pintavalle G, Redaelli V, Achille G, Sciume L, Corbo M. Criterion validity of the instrumented Timed Up and Go test: A partial least square regression study. Gait Posture. 2018 Mar;61:287-293. doi: 10.1016/j.gaitpost.2018.01.015. Epub 2018 Jan 31. — View Citation

Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ. Will my patient fall? JAMA. 2007 Jan 3;297(1):77-86. doi: 10.1001/jama.297.1.77. — View Citation

Picardi M, Redaelli V, Antoniotti P, Pintavalle G, Aristidou E, Sterpi I, Meloni M, Corbo M, Caronni A. Turning and sit-to-walk measures from the instrumented Timed Up and Go test return valid and responsive measures of dynamic balance in Parkinson's disease. Clin Biomech (Bristol, Avon). 2020 Dec;80:105177. doi: 10.1016/j.clinbiomech.2020.105177. Epub 2020 Sep 18. — View Citation

Reinhard C, Bachoud-Levi AC, Baumer T, Bertini E, Brunelle A, Buizer AI, Federico A, Gasser T, Groeschel S, Hermanns S, Klockgether T, Krageloh-Mann I, Landwehrmeyer GB, Leber I, Macaya A, Mariotti C, Meissner WG, Molnar MJ, Nonnekes J, Ortigoza Escobar JD, Perez Duenas B, Renna Linton L, Schols L, Schuele R, Tijssen MAJ, Vandenberghe R, Volkmer A, Wolf NI, Graessner H. The European Reference Network for Rare Neurological Diseases. Front Neurol. 2021 Jan 14;11:616569. doi: 10.3389/fneur.2020.616569. eCollection 2020. — View Citation

Scarano S, Rota V, Tesio L, Perucca L, Robecchi Majnardi A, Caronni A. Balance Impairment in Fahr's Disease: Mixed Signs of Parkinsonism and Cerebellar Disorder. A Case Study. Front Hum Neurosci. 2022 Mar 9;16:832170. doi: 10.3389/fnhum.2022.832170. eCollection 2022. — View Citation

Scarano S, Sansone VA, Ferrari Aggradi CR, Carraro E, Tesio L, Amadei M, Rota V, Zanolini A, Caronni A. Balance impairment in myotonic dystrophy type 1: Dynamic posturography suggests the coexistence of a proprioceptive and vestibular deficit. Front Hum Neurosci. 2022 Jul 28;16:925299. doi: 10.3389/fnhum.2022.925299. eCollection 2022. — View Citation

The Lancet Neurology. Rare neurological diseases: a united approach is needed. Lancet Neurol. 2011 Feb;10(2):109. doi: 10.1016/S1474-4422(11)70001-1. No abstract available. Erratum In: Lancet Neurol. 2011 Mar;10(3):205. — View Citation

Vieira ER, Palmer RC, Chaves PH. Prevention of falls in older people living in the community. BMJ. 2016 Apr 28;353:i1419. doi: 10.1136/bmj.i1419. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Balance (Mini-BESTest)	Mini Balance Evaluation Systems Test (Mini-BESTest, an ordinal score of balance)	At enrollment
Primary	Balance (Timed Up and Go test)	Timed Up and Go test instrumented with inertial sensors	At enrollment
Primary	Gait speed	10 m walking test	At enrollment
Primary	Gait analysis - kinematic - stride length	Stride length, right step length and left step length	At enrollment
Primary	Gait analysis - kinematic - duration	Stride duration, right and left step duration	At enrollment
Primary	Gait analysis - kinematic - width of the base of support	Width of the base of support	At enrollment
Primary	Gait analysis - kinematic - dorsal ankle angle	Dorsal ankle angle	At enrollment
Primary	Gait analysis - dynamic - reaction force	Anterior-posterior, mediolateral and vertical reaction force	At enrollment
Primary	Gait analysis - dynamic - ankle power	Right and left ankle power	At enrollment
Primary	Gait analysis - dynamic - energy	Potential and kinetic energy of the body centre of mass	At enrollment
Primary	Posturography - static - centre of pressure position	Centre of pressure position while standing	At enrollment
Primary	Posturography - static - centre of mass position	Centre of mass position while standing	At enrollment
Primary	Posturography - dynamic - centre of pressure position	Centre of pressure position after base of support perturbations	At enrollment
Primary	Posturography - dynamic - centre of mass position	Centre of mass position after base of support perturbations	At enrollment