Clinical Implications of FKBP5 in Stroke

• Sponsor: Taipei Veterans General Hospital, Taiwan (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05198037
• Collaborator: (none)
• Enrollment: 500
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 44
• Patients Per Site Per Month: 11.4

Study Details

Study Description

Brief Summary

With contemporary lifestyle changes and global aging, it is important yet unknown how stress interacts to post-stroke outcomes. This proposal aims to study the link between the stress-responsive FKBP51-related pathways and neural plasticity after stroke, elucidating FKBP5 gene polymorphisms and blood FKBP51 regulation in relation to brain excitability and functions, understanding the effects of transcranial direct current stimulation, and characterizing brain mechanisms for individualized early rehabilitation after stroke.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Device: Bihemispheric tDCS	N/A

Detailed Description

Stress is an underestimated risk factor and also a consequence of cardiovascular diseases and stroke. FK506-binding protein 51 (FKBP51) modulates stress responses by acting as a co-chaperone that negatively regulates glucocorticoid receptor (GR) to cortisol binding and nuclear signaling. In an oxygen-glucose deprivation (OGD) model of acute mouse hippocampal slices, FKBP5 deletion reduced ischemic neuronal hyperexcitation, and cathodal electrical stimulation of OGD-injured wild-type decreased FKBP51 levels. However, clinical implications of FKBP5 polymorphisms and FKBP51 regulation in post-stroke outcomes and neuromodulation-induced plasticity are unknown. We aim to assess the link between FKBP5 polymorphisms and blood FKBP51 regulation after stroke, and their relationship with stroke phenotypes, brain connectivity and functional outcomes.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Anticipated 100 participants are assigned to the experimental or sham-controlled groups with an allocation rate of 1:1, for the clinical trial. In addition, another group of patients participates in the observational study (no intervention).Anticipated 100 participants are assigned to the experimental or sham-controlled groups with an allocation rate of 1:1, for the clinical trial. In addition, another group of patients participates in the observational study (no intervention).
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Clinical Implications of FKBP5 in Post-stroke Neural Plasticity and Neuromodulation Effects
• Actual Study Start Date: Nov 1, 2021
• Anticipated Primary Completion Date: Jul 1, 2025
• Anticipated Study Completion Date: Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active transcranial direct current stimulation (tDCS) Weak direct currents with 2 mA are delivered 20 minutes per session (including 30s ramp-up and 30s ramp-down) during tailored upper extremity task practice. Total sessions are 20 over 10 days.	Device: Bihemispheric tDCS; The anode and cathode are placed over the ipsilesional and contralesional primary motor cortex (C3 or C4 based on 10-20 system), respectively. The size of the electrode is 5x5 cm.
Sham Comparator: Sham tDCS The device is automatically shut down after 2-minute stimulation. Treatment sessions and frequency are the same as the Experimental arm.	Device: Bihemispheric tDCS; The anode and cathode are placed over the ipsilesional and contralesional primary motor cortex (C3 or C4 based on 10-20 system), respectively. The size of the electrode is 5x5 cm.

Outcome Measures

Primary Outcome Measures

1. Fugl-Meyer Assessment of Upper Extremity, FMA-UE [Change score from baseline (~10 days poststroke) to 90 days poststroke]

   Motor recovery of upper extremity poststroke

Secondary Outcome Measures

1. Action Research Arm Test, ARAT [Change score from baseline (~10 days poststroke) to 90 days poststroke]

   Motor function of upper extremity poststroke

2. Fugl-Meyer Assessment of Lower Extremity, FMA-LE [Change score from baseline (~10 days poststroke) to 90 days poststroke]

   Motor recovery of lower extremity poststroke

3. Perceived Stress Scale-10 [Change score from baseline (~10 days poststroke) to 90 days poststroke]

   Stress level poststroke

4. Protein and gene test [Change score from baseline (~10 days poststroke) to 90 days poststroke]

   Protein expression poststroke and identifying genotypes of participants

Other Outcome Measures

1. Resting-state structural and functional connectivity by magnetic resonance imaging [Change score from baseline (~10 days poststroke) to 90 days poststroke]

   Connectivity-level plasticity post-intervention/poststroke

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Unilateral ischemic or hemorrhagic stroke

• Aged 20-80 years old

Exclusion Criteria:

• FMA-UE is over 49 points

• Major psychiatric diseases

• Major neurologic diseases

• Global aphasia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Taipei Veterans General Hospital	Taipei City		Taiwan	112

Sponsors and Collaborators

• Taipei Veterans General Hospital, Taiwan

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Taipei Veterans General Hospital, Taiwan
• ClinicalTrials.gov Identifier: NCT05198037
• Other Study ID Numbers: 2021-02-002C
• First Posted: Jan 20, 2022
• Last Update Posted: Jan 20, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Taipei Veterans General Hospital, Taiwan: Stroke; FKBP5; Motor; Transcranial direct current stimulation; Plasticity; Stress
• Additional relevant MeSH terms: Stroke

Study Results

No Results Posted as of Jan 20, 2022