CNS Changes Following Upper Limb Loss

Functional, Structural, and Metabolic Central Nervous System Changes Following Damage of the Central Nervous System

The objective of this study is to better understand the structural and functional changes that the central nervous system (CNS) undergoes following congenital upper limb loss. The focus is on the brain's sensory processing and how neuronal changes may relate to clinical measures. By doing so, the hope is to gain insight into the contribution of critical periods to the plasticity of the sensorimotor processing stream. Both macroscopic and microscopic changes of the brain will be examined in individuals with upper limb amelia and compared to healthy controls. fMRI will be combined with behavioural testing to understand which clinical and behavioural determinants drive somatosensory representations along the entire somatosensory processing stream. Using advanced imaging techniques, the aim is to investigate the contribution of brainstem reorganisation to plasticity observed at the cortical level and, by doing so, gain a better understanding of the mechanistic underpinnings of functional reorganisation. Overall, the hope is to provide the first mechanistic insight into whether early life experiences are crucial for the development of the relay nuclei in the central nervous system and how these changes relate to clinical measures such as adaptive behaviours or pain.

Study Overview

• Status: Recruiting
• Conditions: Amputation, Congenital; Upper Limb; Amelia
• Intervention / Treatment: Diagnostic test: MRI; Diagnostic test: MRI

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Paige Howell, PhD; Phone Number: +41 44 632 32 94; Email: paige.howell@hest.ethz.ch
• Study Contact Backup: Name: Sanne Kikkert; Phone Number: +41 44 632 32 94; Email: sanne.kikkert@balgrist.ch

Study Locations

• Switzerland
  • Canton of Zurich
    • Zurich, Canton of Zurich, Switzerland, 8008
      • Recruiting
      • Balgrist Campus
      • Contact: Paige Howell, PhD; Phone Number: +41 44 632 32 94; Email: paige.howell@hest.ethz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with an upper-limb amputation and healthy subjects.

Description

Inclusion Criteria - Patients:

• Age 18-75
• Upper-limb congenital amputees with complete absence of a hand
• Signed informed consent

Exclusion Criteria - Patients:

• Contraindications to magnetic resonance imaging
• Neurological impairment of body function impairments not induced by spinal cord injury
• BMI > 40
• Pregnancy
• Claustrophobia

Inclusion Criteria - Healthy subjects:

• Age 18-75
• Signed Informed consent

Exclusion Criteria - Healthy subjects:

• Contraindications to magnetic resonance imaging
• Pregnancy
• Neurological illness
• Impairment of body function induced by a congenital upper-limb amputation
• Claustrophobia
• BMI > 40

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy subjects	Diagnostic test: MRI; Use of functional and structural MRI in both the brain and the spinal cord as well as questionnaires and clinical measures of motor function; Diagnostic test: MRI; Use of functional and structural MRI in both the brain and the spinal cord and questionnaires.
Patients with congenital amputation	Diagnostic test: MRI; Use of functional and structural MRI in both the brain and the spinal cord as well as questionnaires and clinical measures of motor function; Diagnostic test: MRI; Use of functional and structural MRI in both the brain and the spinal cord and questionnaires.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of functional MRI (fMRI) parameter between 2 to 4 time points	Change of brain activities is assessed between 2 to 4 time points using fMRI during resting-state or a specific task in patients with congenital amputations and compared to healthy controls	Up to 50 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conventional magnetic resonance imaging (MRI) parameter	Structural characteristics in the brain and cervical spinal cord are assessed in patients with congenital upper-limb amputations using conventional MRI and compared to healthy controls	Up to 50 weeks
Amputees: Motor Activity Log questionnaire	Evaluation of residual limb and/or prosthesis usage as compared to other body parts via a questionnaire and behavioural assessments.	Up to 50 weeks

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: ETH Zurich
• Investigators: Principal Investigator: Patrick Freund, Prof., University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: September 12, 2023
• First Submitted That Met QC Criteria: September 12, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Hand; Functional MRI; Plasticity; Congenital amputee; Upper limb amelia; Somatotopy; Reorganisation
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Musculoskeletal Abnormalities; Congenital Abnormalities; Limb Deformities, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amputation, Congenital; Ectromelia
• Other Study ID Numbers: 2018-00937 - Upper Limb Loss

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No