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

Trial Summary

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.

What evidence supports the effectiveness of the drug fluoxetine for treating genetic disorders?

Fluoxetine has shown effectiveness in treating various conditions such as anxiety disorders, obsessive-compulsive disorder, and disruptive behavior disorders in children, which suggests it may have potential benefits for other conditions, including genetic disorders. In children with autism, fluoxetine was found to have a good response in a significant number of cases, especially when there was a family history of mood disorders. ^{1 2 3 4 5}

Is fluoxetine generally safe for humans?

Fluoxetine, also known as Prozac, is generally safe and well-tolerated in humans. Common side effects include stomach and nervous system issues, and it is considered safe for long-term use, even during pregnancy, with no major withdrawal symptoms. However, it may cause some developmental effects during pregnancy and reversible sexual function issues in adults. ^{6 7 8 9 10}

How is the drug fluoxetine unique for treating a genetic disorder?

Fluoxetine is unique because it is primarily known as an antidepressant that works by increasing serotonin levels in the brain, and it is the only approved drug for major depressive disorder in children and adolescents. Its use for a genetic disorder is novel, as it is not typically associated with treating genetic conditions. ^{10 11 12 13 14}

What is the purpose of this trial?

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.

Research Team

Danielle Baribeau, MD, PhD

Principal Investigator

Holland Bloorview Kids Rehabilitation Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement. [2019]

2. Belgium pubmed.ncbi.nlm.nih.gov

[Assessment of the clinical activity of fluoxetin (Prozac) according of the "Stars of Liège" model]. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Fluoxetine for the treatment of childhood anxiety disorders: open-label, long-term extension to a controlled trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Clinical characteristics of response to fluoxetine treatment of obsessive-compulsive disorder. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Neural Responses to Fluoxetine in Youths with Disruptive Behavior and Trauma Exposure: A Pilot Study. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The fetal safety of fluoxetine: a systematic review and meta-analysis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Fluoxetine: a suitable long-term treatment. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events and outcome in a clinical trial of fluoxetine for major depressive disorder. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Safety and side effect profile of fluoxetine. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Fluoxetine. [2005]

11. United States pubmed.ncbi.nlm.nih.gov

Fluoxetine in the Management of Major Depressive Disorder in Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials. [2022]

12. England pubmed.ncbi.nlm.nih.gov

A randomized double-blind clinical trial on analgesic efficacy of fluoxetine for persistent somatoform pain disorder. [2013]

13. India pubmed.ncbi.nlm.nih.gov

Fluoxetine induced hypomania - a case report. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Cardiac and hepatic side effects of fluoxetine in male and female adolescent rats. [2023]