Fluoxetine for Genetic Disorder

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Holland Bloorview Kids Rehabilitation Hospital

Must not be taking: MAOIs, SSRIs, Tricyclics, others

Disqualifiers: Hypersensitivity to fluoxetine, Long QT, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests fluoxetine, a medication typically used for mood disorders, to determine if it can improve developmental outcomes in a child with a KCNC1-related disorder, which affects brain function. The study will compare the child's response to fluoxetine versus a placebo (a non-active substance) over several weeks. It is specifically for a child who can take daily oral medication and is in good general health. Holland Bloorview Kids Rehabilitation Hospital will conduct the trial using a special design that randomly alternates between placebo and the real drug.

As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

Will I have to stop taking my current medications?

You may need to stop taking certain medications. If you are currently using monoamine oxidase inhibitors, other selective serotonin reuptake inhibitors, tricyclic antidepressants, or drugs that affect metabolism through specific enzymes, you cannot participate in the trial.

Is there any evidence suggesting that fluoxetine is likely to be safe for humans?

Research has shown that fluoxetine is generally safe for use. Studies examining its effects on cells have found no harmful changes. Some common side effects of fluoxetine are linked to genetics, making certain individuals more susceptible to them.

Fluoxetine, a well-known antidepressant, has been used for a long time, providing extensive information about its safety. However, like many medications, it can cause side effects such as nausea, dizziness, or trouble sleeping. Awareness of the risks related to pregnancy and newborns when using fluoxetine is also important.

Overall, evidence supports that fluoxetine is well-tolerated by many, but individual experiences with side effects can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Fluoxetine is unique because it is traditionally used as an antidepressant but is now being explored for a genetic disorder. Researchers are excited about this treatment because fluoxetine works by increasing the levels of serotonin in the brain, which could address symptoms of the disorder differently than existing treatments. Unlike the current standard care options, which may not specifically target serotonin levels, fluoxetine offers a potential new mechanism of action. This novel approach could open up possibilities for more effective symptom management for those with the genetic disorder.

What evidence suggests that fluoxetine might be an effective treatment for KCNC1-related disorder?

Research has shown that fluoxetine, commonly used to treat depression, helps by boosting serotonin levels in the brain. Serotonin is a chemical that enhances mood and emotional stability. One study found that genetic differences can affect fluoxetine's effectiveness, but these differences usually don't alter the required dose or the treatment's success. While primarily an antidepressant, fluoxetine has also been studied for other uses due to its effects on brain chemistry. This trial examines its potential benefits for developmental outcomes in a specific genetic disorder. Participants will undergo a sequence of treatments, starting with a placebo, then fluoxetine, and returning to placebo, to assess its effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Danielle Baribeau, MD, PhD

Principal Investigator

Holland Bloorview Kids Rehabilitation Hospital

Are You a Good Fit for This Trial?

This trial is for a child with KCNC1-related disorder, which is a rare genetic condition that can cause epileptic encephalopathy. The study will take place at Holland Bloorview Kids Rehabilitation Hospital and aims to improve developmental outcomes.

Inclusion Criteria

Consent provided by substitute decision maker

In good general health as evidenced by medical history

My recent blood tests show my liver, kidneys, and potassium levels are normal.

Exclusion Criteria

Hypersensitivity to fluoxetine or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container

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

I am currently taking certain antidepressants or drugs that affect my body's drug processing enzymes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Placebo Phase

Participants receive placebo (medical grade cornstarch in a gel capsule, 1 capsule daily)

Approximately 10-14 weeks

Fluoxetine Treatment

Participants receive active fluoxetine (2.5 then 5 mg po daily)

Approximately 10-14 weeks

Return to Placebo

Participants return to placebo (medical grade cornstarch in a gel capsule, 1 capsule daily)

Approximately 10-14 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fluoxetine

Trial Overview

The trial tests oral powdered fluoxetine over approximately 8 to 10 months using an ABA phase design where the patient receives placebo, then fluoxetine, and back to placebo. The exact times when active treatment starts and stops are chosen randomly but kept secret.

How Is the Trial Designed?

Group I: Placebo-Fluoxetine-Placebo Experimental Treatment 1 Intervention

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

Fluoxetine is already approved in United States, European Union for the following indications:

Approved in United States as Prozac for:

• Depression
• Anxiety
• Obsessive-compulsive disorder
• Bulimia nervosa
• Panic disorder

Approved in European Union as Prozac for:

• Major depressive episodes
• Obsessive-compulsive disorder
• Bulimia nervosa

Who Is Running the Clinical Trial?

Holland Bloorview Kids Rehabilitation Hospital

Lead Sponsor

Trials

69

Recruited

14,100+

The Hospital for Sick Children

Collaborator

Trials

724

Recruited

6,969,000+

Published Research Related to This Trial

A systematic review of 21 studies found that fluoxetine use during the first trimester of pregnancy does not significantly increase the risk of major fetal malformations, with an odds ratio of 1.12, indicating safety for the fetus.

However, there is a noted increased risk of cardiac malformations associated with fluoxetine use, with an odds ratio of 1.6 from cohort studies, suggesting that this risk may be influenced by factors such as ascertainment bias in reporting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fetal safety of fluoxetine: a systematic review and meta-analysis. Riggin, L., Frankel, Z., Moretti, M., et al.[2022]

In a study of 384 depressed outpatients treated with fluoxetine over 8 weeks, the occurrence of treatment-related adverse events (TRAEs) did not predict treatment response or premature discontinuation of the medication.

Despite monitoring for somatic complaints and classifying them as TRAEs, the results indicated that these side effects had no significant impact on the effectiveness of fluoxetine in treating major depressive disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events and outcome in a clinical trial of fluoxetine for major depressive disorder. Papakostas, GI., Petersen, T., Denninger, JW., et al.[2019]

Fluoxetine is generally safe and well-tolerated for treating depression and other neuropsychiatric disorders, with common side effects primarily affecting the gastrointestinal and nervous systems at the recommended dose of 20 mg/day.

Its long half-life reduces the risk of withdrawal symptoms, but fluoxetine can interact with other medications due to its inhibition of certain liver enzymes, although most interactions are not clinically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and side effect profile of fluoxetine. Wernicke, JF.[2022]

Fluoxetine (Prozac) at a daily dose of 20 mg was rated by psychiatrists as having a moderate antidepressant effect, comparable to other antidepressants like amitriptyline and clomipramine, but with weak psychostimulant and anxiolytic effects.

The medication showed very weak sedative effects and lacked anticholinergic and hypotensive side effects, although moderate digestive side effects were noted, indicating a generally favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Assessment of the clinical activity of fluoxetin (Prozac) according of the "Stars of Liège" model]. Ansseau, M., Bataille, M., Bobon, D., et al.[2013]

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Prozac® (Fluoxetine Hydrochloride) - SDS US - Eli Lilly

Material is stable under normal conditions. Chemical stability. Hazardous polymerization does not occur. Possibility of hazardous reactions.

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The data from the present study are important because they confirm the safe use of fluoxetine by humans. In this sense, considering that A. cepa root cells ...

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Potential adverse events of fluoxetine: a real-world study ...

Post-market spontaneous reporting data can offer further insight into drug safety. Risks related to pregnancy, the fetus, and neonates.