Fluoxetine in KCNC1-related Disorder

A Single Patient Trial of Fluoxetine in KCNC1-related Disorder

This is a single patient study of oral powdered fluoxetine to target developmental outcomes in a child with KCNC1-related disorder. This trial will be conducted at Holland Bloorview Kids Rehabilitation Hospital over 32 to 42 weeks, using a quasi experimental ABA phase design (placebo-fluoxetine-placebo) with randomized and blinded active treatment start and stop moments.

Study Overview

• Status: Completed
• Conditions: Rare Diseases; Genetic Disease; KCNC1 Related Disorder
• Intervention / Treatment: Drug: Fluoxetine

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1R8
      • Holland Bloorview Kids Rehabilitation Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Consent provided by substitute decision maker.
2. In good general health as evidenced by medical history
3. Screening baseline bloodwork (or availability of clinical bloodwork within 3 months of trial start) with values below relevant cut-offs for adequate hepatic and renal function, and baseline electrolytes including potassium within normal range.
4. Ability to take oral medication and be willing to adhere to the daily oral medication regimen

Exclusion Criteria:

1. Current use of monoamine oxidase inhibitors, other selective serotonin reuptake inhibitors, tricyclic antidepressants, or agents that strongly affect metabolism via CYP2D6, CYP2C9 or CYP3A4.
2. Hypersensitivity to fluoxetine or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container
3. Treatment with another investigational drug or other medication intervention within 8 weeks of starting the trial.
4. Any condition or diagnosis, that could in the opinion of the Principal Investigator or delegate interfere with the participant's ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk.
5. Long QT syndrome including acquired long QT syndrome (e.g., due to concomitant use of a drug that prolongs the QT); a family history of QT prolongation; or other clinical conditions that predispose to arrhythmias.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo-Fluoxetine-Placebo; placebo (medical grade cornstarch in a gel capsule, 1 capsule daily), followed by blinded randomized cross-over moment to active fluoxetine (2.5 then 5 mg po daily), followed by blinded randomized cross-over moment back to placebo	Drug: Fluoxetine; Oral fluoxetine daily, 2.5 to 5 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor development	Parent report on the Early Motor Questionnaire	Weekly from date of randomization to up to 42 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Adverse event reporting	From date of randomization to up to 42 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adaptive skills	Vineland Adaptive Behavior Scale	Week 1, 13, 29 and 37
Cognitive skills	Mullen Scales of Early Learning	Week 1, 13, 29 and 37
Family priority outcome targets	Measure Your Own Medical Profile- 2	Weekly from date of randomization to up to 42 weeks
Clinical Global Impression- Improvement Scale (CGI-I)	Clinician assessment of overall development	Every 4 weeks from date of randomization to up to 42 weeks

Collaborators and Investigators

• Sponsor: Holland Bloorview Kids Rehabilitation Hospital
• Collaborators: The Hospital for Sick Children
• Investigators: Principal Investigator: Danielle Baribeau, MD, PhD, Holland Bloorview Kids Rehabilitation Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2024
• Primary Completion (Actual): November 28, 2024
• Study Completion (Actual): November 28, 2024

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Actual): July 2, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Rare Diseases; Genetic Diseases, Inborn; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Cytochrome P-450 Enzyme Inhibitors; Neurotransmitter Uptake Inhibitors; Antidepressive Agents; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine
• Other Study ID Numbers: 2023-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Single patient trial; would be challenging to de-identify.

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