Establishing a Core Outcome Set for Creatine Transporter Deficiency and Guanidinoacetate Methyltransferase Deficiency

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Creatine transporter (CTD) and guanidinoacetate methyltransferase (GAMT) deficiencies cause cerebral creatine deficiency, leading to severe intellectual and developmental disabilities.
• Current management for GAMT is lifelong and burdensome, while CTD lacks effective treatments.
• A lack of standardized, patient-relevant outcomes hinders drug development for these rare metabolic disorders.

Purpose of the Study:

• To establish the first core outcome set (COS) for CTD and GAMT deficiencies, incorporating patient and caregiver perspectives.
• To ensure clinical trials measure outcomes that are meaningful to patients and stakeholders.
• To facilitate comparable clinical trial results and accelerate drug development.

Main Methods:

• Collaborative development of a COS involving caregivers and health professionals.
• Identification of key outcomes relevant to CTD and GAMT patients.
• Consensus-building for outcome selection in clinical research.

Main Results:

• A comprehensive COS was established, including seven core outcomes for both CTD and GAMT: Adaptive Functioning, Cognitive Functioning, Emotional Dysregulation, MRS Brain Creatine, Seizure/Convulsions, Expressive Communication, and Fine Motor Functions.
• An additional outcome, Serum/Plasma Guanidinoacetate, was included specifically for GAMT.
• Caregiver involvement enhanced community engagement and empowerment.

Conclusions:

• The developed COS provides a patient-centered framework for clinical trials in CTD and GAMT.
• This standardized approach is expected to improve the efficiency and comparability of research, ultimately accelerating the development of treatments.
• Prioritizing patient and caregiver perspectives in outcome selection is crucial for rare disease research.