Harmonic Ratio in Patients With GLUT1 Deficiency Syndrome

NCT05887739 | Active Not Recruiting

• 1 other identifier: Gait analysis in GLUT1DS
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

Glucose transporter deficiency syndrome type 1 (GLUT1DS) is a rare, genetically determined, neurometabolic disorder . It is estimated that about 90% of affected patients present various pathological gait patterns. Ataxic, spastic, ataxo-spastic, or dystonic walking are the main manifestations described to date. The kinematic gait analysis with inertial sensors represents a method that is easily applicable in clinical practice, with possible application in numerous neurological syndromes of the pediatric and adult age. Through the kinematic gait analysis, it will be possible to obtain an accurate characterization of the gait of patients with GLUT1DS. This will allow, in the first place, a better knowledge of locomotor parameters in this rare cohort of patients. Given that kinematic analysis through a wearable sensor is a method that can be easily integrated into daily clinical practice, the data obtained could become prognostic biomarkers and significant outcome measures of the disease (also in relation to possible improvements deriving from treatment with a ketogenic diet or in the context of future pharmacological trials).

Conditions

GLUT1DS1; Dystonia; Gait Disorders, Neurologic; Gait Ataxia

Outcome Measures

Primary Outcomes (2)

• Comparison of Harmonic Ratio between patients and healthy controls at baseline

  The primary outcome will be the difference in Harmonic Ratio (HR - continuous variable, without unit of measurement) between patients and healthy controls at baseline

  Single evaluation at baseline (V1)

• Comparison of largest Lyapunov exponent between patients and healthy controls at baseline

  A co-primary outcome will be the difference in largest Lyapunov exponent (LLE - continuous variable, without unit of measurement) between patients and healthy controls at baseline

  Single evaluation at baseline (V1)

Secondary Outcomes (10)

• Comparison of coefficient of variation between patients and healthy controls at baseline

  Single evaluation at baseline (V1)

• Comparison of normalized jerk score between patients and healthy controls at baseline

  Single evaluation at baseline (V1)

• Comparison of recurrence quantification analysis between patients and healthy controls at baseline

  Single evaluation at baseline (V1)

• Comparison of Multiscale entropy between patients and healthy controls at baseline

  Single evaluation at baseline (V1)

• Comparison of Harmonic Ratio in patients between subsequent visits

  Change from baseline (V1) to 6 months after (V2) to 12 months after (V3) to 18 months after (V4) to 24 months after (V5)

Study Arms (2)

GLUT1DS

Patients affected by GLUT1 deficiency syndrome

Diagnostic Test: Inertial gait analysis

Healthy controls

Age and sex matched healthy controls

Diagnostic Test: Inertial gait analysis

Interventions

Inertial gait analysis DIAGNOSTIC_TEST

All groups will be evaluated with inertial gait analysis

GLUT1DS; Healthy controls

Eligibility Criteria

• Age: 3 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients affected by GLUT1 deficiency syndromes will be enrolled by attending our clinic at the IRCCS Mondino Foundation. Healthy controls will be age and sex matched people among relatives and caregivers of the patients attending our clinic.

You may qualify if:

• Pediatric and adult patients (range 3-60 years) diagnosed with GLUT1 deficiency syndrome according to the recommendations of the International Study Group (Klepper et al., 2020)
• Ability to walk independently the necessary route
• Compliance with study procedures

You may not qualify if:

• Presence of other neurological or orthopedic comorbidities that may influence gait assessment
• Poor compliance with study procedures
• Healthy controls eligibility criteria:
• Typically developing healthy volunteers
• Age range 3-60 years
• Presence of neurological or orthopedic comorbidities that may influence gait assessment

Sponsors & Collaborators

• IRCCS National Neurological Institute "C. Mondino" Foundation: lead
• University of Roma La Sapienza: collaborator

Study Sites (2)

Child and Adolescent Epileptology Center

Pavia, 27100, Italy

Location

Headache Science & Neurorehabilitation Center

Pavia, 27100, Italy

Location

Related Publications (12)

• Alter AS, Engelstad K, Hinton VJ, Montes J, Pearson TS, Akman CI, De Vivo DC. Long-term clinical course of Glut1 deficiency syndrome. J Child Neurol. 2015 Feb;30(2):160-9. doi: 10.1177/0883073814531822. Epub 2014 Apr 30.

  PMID: 24789115 BACKGROUND

• Bisi MC, Di Marco R, Ragona F, Darra F, Vecchi M, Masiero S, Del Felice A, Stagni R. Quantitative Characterization of Motor Control during Gait in Dravet Syndrome Using Wearable Sensors: A Preliminary Study. Sensors (Basel). 2022 Mar 10;22(6):2140. doi: 10.3390/s22062140.

  PMID: 35336311 BACKGROUND

• Blumenschine M, Montes J, Rao AK, Engelstad K, De Vivo DC. Analysis of Gait Disturbance in Glut 1 Deficiency Syndrome. J Child Neurol. 2016 Nov;31(13):1483-1488. doi: 10.1177/0883073816661662. Epub 2016 Aug 10.

  PMID: 27511993 BACKGROUND

• Castiglia SF, Tatarelli A, Trabassi D, De Icco R, Grillo V, Ranavolo A, Varrecchia T, Magnifica F, Di Lenola D, Coppola G, Ferrari D, Denaro A, Tassorelli C, Serrao M. Ability of a Set of Trunk Inertial Indexes of Gait to Identify Gait Instability and Recurrent Fallers in Parkinson's Disease. Sensors (Basel). 2021 May 15;21(10):3449. doi: 10.3390/s21103449.

  PMID: 34063468 BACKGROUND

• Castiglia SF, Trabassi D, Tatarelli A, Ranavolo A, Varrecchia T, Fiori L, Di Lenola D, Cioffi E, Raju M, Coppola G, Caliandro P, Casali C, Serrao M. Identification of Gait Unbalance and Fallers Among Subjects with Cerebellar Ataxia by a Set of Trunk Acceleration-Derived Indices of Gait. Cerebellum. 2023 Feb;22(1):46-58. doi: 10.1007/s12311-021-01361-5. Epub 2022 Jan 26.

  PMID: 35079958 BACKGROUND

• Castiglia SF, Trabassi D, De Icco R, Tatarelli A, Avenali M, Corrado M, Grillo V, Coppola G, Denaro A, Tassorelli C, Serrao M. Harmonic ratio is the most responsive trunk-acceleration derived gait index to rehabilitation in people with Parkinson's disease at moderate disease stages. Gait Posture. 2022 Sep;97:152-158. doi: 10.1016/j.gaitpost.2022.07.235. Epub 2022 Jul 21.

  PMID: 35961132 BACKGROUND

• De Giorgis V, Varesio C, Baldassari C, Piazza E, Olivotto S, Macasaet J, Balottin U, Veggiotti P. Atypical Manifestations in Glut1 Deficiency Syndrome. J Child Neurol. 2016 Aug;31(9):1174-80. doi: 10.1177/0883073816650033. Epub 2016 Jun 1.

  PMID: 27250207 BACKGROUND

• Klepper J, Leiendecker B. GLUT1 deficiency syndrome--2007 update. Dev Med Child Neurol. 2007 Sep;49(9):707-16. doi: 10.1111/j.1469-8749.2007.00707.x.

  PMID: 17718830 BACKGROUND

• Klepper J, Akman C, Armeno M, Auvin S, Cervenka M, Cross HJ, De Giorgis V, Della Marina A, Engelstad K, Heussinger N, Kossoff EH, Leen WG, Leiendecker B, Monani UR, Oguni H, Neal E, Pascual JM, Pearson TS, Pons R, Scheffer IE, Veggiotti P, Willemsen M, Zuberi SM, De Vivo DC. Glut1 Deficiency Syndrome (Glut1DS): State of the art in 2020 and recommendations of the international Glut1DS study group. Epilepsia Open. 2020 Aug 13;5(3):354-365. doi: 10.1002/epi4.12414. eCollection 2020 Sep.

  PMID: 32913944 BACKGROUND

• Pearson TS, Akman C, Hinton VJ, Engelstad K, De Vivo DC. Phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1 DS). Curr Neurol Neurosci Rep. 2013 Apr;13(4):342. doi: 10.1007/s11910-013-0342-7.

  PMID: 23443458 BACKGROUND

• Suzuki T, Ito Y, Ito T, Kidokoro H, Noritake K, Hattori A, Nabatame S, Natsume J. Quantitative Three-Dimensional Gait Evaluation in Patients With Glucose Transporter 1 Deficiency Syndrome. Pediatr Neurol. 2022 Jul;132:23-26. doi: 10.1016/j.pediatrneurol.2022.04.012. Epub 2022 Apr 29.

  PMID: 35605310 BACKGROUND

• Mehdizadeh S. The largest Lyapunov exponent of gait in young and elderly individuals: A systematic review. Gait Posture. 2018 Feb;60:241-250. doi: 10.1016/j.gaitpost.2017.12.016. Epub 2017 Dec 16.

  PMID: 29304432 BACKGROUND

MeSH Terms

Conditions

Dystonia; Gait Disorders, Neurologic; Gait Ataxia

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Ataxia

Study Officials

• Roberto De Icco

  IRCCS, Mondino Foundation

  PRINCIPAL INVESTIGATOR

• Valentina De Giorgis

  IRCCS, Mondino Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2023
• First Posted: June 5, 2023
• Study Start: January 1, 2023
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 30, 2024

Record last verified: 2024-04

Locations

IT (2)