Cognitive Function in Rett Syndrome During Trofinetide Treatment

Assessing cognitive functions among individuals with severe intellectual and developmental disabilities (IDD), including RTT, is often challenging due to floor effects of many standardized assessment batteries in this population. In addition, deficits in motor function and verbal ability may obscure certain abilities in this population when using standard IQ measures. Remote eye-tracking tasks have been proposed as an alternative approach for assessing cognitive functions among individuals with severe IDD, because eye-tracking tasks can be designed to minimize the influence of gross motor and receptive language deficits on performance. Although several types of eye-tracking tasks have been evaluated in RTT, most have been implemented only at a single time-point. As a result, it is unclear whether these measures are stable over time, or sensitive to developmental changes or alterations to health status that occur in RTT (e.g., developmental regression, development of seizures, change in medication, etc.). With the recent FDA approval of trofinetide for the treatment of RTT, we have a novel opportunity to test the sensitivity of eye-tracking and other psychophysiological measures to treatment changes. Anecdotally, parents and clinicians have reported improvements in attention and alertness during trofinetide treatment, but currently available outcome measures do not capture these types of effects. Therefore, we propose to conduct a pilot trial of changes in measures of attention, oculomotor function, learning, and autonomic function, all collected using non-invasive measures, during trofinetide treatment. This is an observational within-subject design with a 4-week post-treatment assessment compared to two pre-treatment assessments. Additional optional follow-up assessments will be performed with families who are interested and returning for standard-of-care visits to Gillette or who are willing to travel for a research-only visit.

Study Overview

• Status: Recruiting
• Conditions: Rett Syndrome
• Intervention / Treatment: Other: None interventional

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Breanne Byiers; Phone Number: 612-626-7892; Email: byier001@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Recruiting
      • University of Minnesota
      • Contact: Breanne Byiers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Any individuals who are initiating trofinetide treatment for RTT through the physicians associated with the Gillette Children's RTT clinic will be potentially eligible for participation, regardless of age.

Description

Inclusion Criteria:

• Any individuals who are initiating trofinetide treatment for RTT through the physicians associated with the Gillette Children's RTT clinic will be potentially eligible for participation, regardless of age. To enroll, participants must meet the following criteria:

  1. Provision of signed and dated informed consent form by the individual's parent/legal guardian
  2. Stated willingness to comply with all study procedures and availability for the duration of the study
  3. Documented diagnosis of Rett syndrome
  4. Participant is not showing active signs of developmental regression, defined as: no loss or degradation of ambulation within the past 6 months; no loss or degradation of hand function within the past 6 months; and no loss or degradation of verbal or non-verbal communication or social skills in the past 6 months.
  5. Participant's current pharmacological treatment regimen has been stable for at least 4 weeks.
  6. Seeking prescription for trofinetide through the Gillette Children's Rett syndrome clinic

Exclusion Criteria:

1. Diagnosis of a progressive medical or neurological condition that in the opinion of the investigator would interfere with the conduct of the study.
2. Current clinically significant systemic illness that is likely to result in the deterioration of the participant's condition during the study.
3. Participants taking any other investigational drug currently or within the past 30 days.
4. Known, uncorrected visual impairment that would limit the ability to view images during eye-tracking tasks.
5. Severe behavioral problems (i.e., aggression, property destruction, extreme hyperactivity) that would interfere with participation in study activities.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; Patients with Rett Syndrome who are interested in Trofinetide treatment	Other: None interventional; This is an observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Function in Rett Syndrome During Trofinetide Treatment	change in saccade latencies during the 'statistical learning' paradigm	baseline, 6weeks to 12 months
Eye movement gaze fixations	change in duration of gaze fixation to the correct image during the 'Looking While Listening' paradigm.	baseline, 6weeks to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate variability	Change in baseline heart rate variability during sustained attention during eye-tracking tasks.	baseline, 6weeks to 12 months
Heart rate suppression	Change in baseline heart rate suppression during sustained attention during eye-tracking tasks.	baseline, 6weeks to 12 months

Collaborators and Investigators

• Sponsor: University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: November 11, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Actual): November 26, 2024

Study Record Updates

• Last Update Posted (Actual): June 12, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Genetic Diseases, Inborn; Disease; Neurobehavioral Manifestations; Heredodegenerative Disorders, Nervous System; Mental Retardation, X-Linked; Intellectual Disability; Genetic Diseases, X-Linked; Syndrome; Rett Syndrome
• Other Study ID Numbers: 33488

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No