A rule-based, dose-finding design for use in stroke rehabilitation research: methodological development.

Area of Science:

• Neurology
• Rehabilitation Medicine
• Clinical Trial Design

Background:

• Dose-optimization studies are crucial but infrequent in stroke rehabilitation research.
• Establishing optimal therapeutic dosages is essential for effective clinical trials.

Purpose of the Study:

• To develop and evaluate a novel rule-based, dose-finding design for stroke rehabilitation.
• To determine the feasibility of this design in identifying a maximally tolerated dose.

Main Methods:

• A 3+3 rule-based dose-finding design was employed, utilizing a modified Fibonacci sequence for dose escalation/de-escalation.
• The study involved five cohorts of three participants with moderate upper limb paresis post-stroke.
• Dose tolerability and benefit were assessed over a 2-week training period using an electronic adherence counter and motor function outcome measures.

Main Results:

• The study successfully identified distinct daily doses for subsequent cohorts, ranging from 50 to 251 repetitions.
• The maximally tolerated dose for the hand opening exercise task was determined to be 209 repetitions per day.
• The rule-based design proved effective in navigating dose adjustments based on adherence and functional improvement.

Conclusions:

• The developed rule-based dose-finding design is a feasible and effective method for stroke rehabilitation research.
• This approach facilitates the identification of maximally tolerated doses, paving the way for more robust clinical trials.