Antioxidant Cocktail for Rett Syndrome

Overseen By Lisa Genore, HBSc

Age: < 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Holland Bloorview Kids Rehabilitation Hospital

Must not be taking: Fluoxetine, Rett-T components

Disqualifiers: Pregnancy, Serious medical conditions, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new antioxidant treatment, Rett-T, to determine if it improves motor skills in individuals with Rett syndrome, a condition affecting movement and coordination. Researchers aim to assess the safety and effectiveness of Rett-T while monitoring specific biological markers to understand the treatment's mechanism. Participants will receive either the Rett-T treatment or a placebo, a harmless powder resembling the treatment but without active ingredients. The trial seeks female participants, ages 2 to 21, with Rett syndrome who can walk at least a little, even with assistance. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that if you are already taking stable medications or supplements that affect behavior, you must continue on the same dose for at least one month before starting the trial and cannot change them during the study. However, if you are taking fluoxetine, you need to be on a stable dose for six weeks before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Rett-T is being explored as a potential treatment for Rett syndrome, a serious condition with limited treatment options. Although specific safety information for Rett-T is not yet available, its presence in early-stage studies suggests it has passed some initial safety checks in humans. Treatments typically must meet safety standards before reaching this stage.

Participants in past Rett syndrome studies have experienced varied results, but no specific safety issues with Rett-T have been reported so far. The study aims to determine how well Rett-T is tolerated and what side effects it might have. Researchers will closely monitor for any negative reactions or problems during the trial. While data is still being collected, the early testing phase of Rett-T indicates that a basic level of safety has been considered for human trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Rett syndrome?

Rett-T is unique because it uses a specific blend of antioxidants aimed at addressing the oxidative stress believed to contribute to symptoms of Rett Syndrome. Current treatments mainly focus on managing symptoms through medications like anticonvulsants and antipsychotics. Unlike these, Rett-T targets the underlying oxidative stress, offering a novel approach that could potentially improve overall cell function and alleviate symptoms more effectively. Researchers are excited because this mechanism might offer a more direct way to tackle some of the disorder's root causes, potentially leading to better outcomes for patients.

What evidence suggests that Rett-T might be an effective treatment for Rett syndrome?

In this trial, participants will receive either Rett-T, a mix of antioxidants, or a placebo. Studies have shown that Rett-T might benefit people with Rett syndrome. In earlier research, patients who took this mix showed significant improvement in additional health measures. Specifically, 52.9% of patients on the treatment experienced meaningful progress, compared to just 8.3% who took a placebo. The mix includes ingredients like vitamin E, N-acetylcysteine, and alpha-lipoic acid, which are believed to combat oxidative stress, a factor in Rett syndrome. While animal studies yielded promising results, more research with people is needed to confirm these findings. ^{6 7 8 9 10}

Who Is on the Research Team?

Evdokia Anagnostou, MD

Principal Investigator

Holland Bloorview Kids Rehabilitation Hospital

Are You a Good Fit for This Trial?

This trial is for female outpatients aged 2-21 with Rett syndrome who can walk (with or without help). They should be on stable doses of any behavior-affecting meds, except fluoxetine which requires a longer period. Participants need normal lab results and must understand English to complete assessments.

Inclusion Criteria

My current medications for behavior have been stable.

Must have normal laboratory test results at Screening/Baseline, with clinically insignificant abnormal findings

Ability to complete assessments, fluency in English (parent/legal guardian; participant, if verbal)

Exclusion Criteria

Presence of another serious medical condition that might interfere with the study, confound interpretation of results, or endanger well-being

I am taking medications or supplements that contain Rett-T components.

Inability to tolerate venipuncture procedures for blood sampling

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Rett-T or placebo for 8 weeks, followed by a 2-week washout period, and then switch to the other treatment for another 8 weeks

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Rett-T

Trial Overview The study tests 'Rett-T,' an antioxidant cocktail, against a placebo to see if it helps with Rett syndrome's core motor issues. It also looks at safety and how the body responds to treatment by checking biological markers.

How Is the Trial Designed?

Group I: Rett T Active Control 1 Intervention

Rett T is a powder for oral suspension. Dosage is dependent on weight. For participants weighing \<30 kg, a 4 g dose (i.e., one 4 g sachet) is intended to be administered orally once a day after dissolving in approximately 125 mL of water. For participants weighing ≥30 kg, a 8 g dose (i.e., two 4 g sachets) is intended to be administered orally once a day after dissolving in approximately 250 mL of water.

Group II: Placebo Placebo Group 1 Intervention

Placebo is a powder for oral suspension. Dosage is dependent on weight. For participants weighing \<30 kg, a 4 g dose (i.e., one 4 g sachet) is intended to be administered orally once a day after dissolving in approximately 125 mL of water. For participants weighing ≥30 kg, a 8 g dose (i.e., two 4 g sachets) is intended to be administered orally once a day after dissolving in approximately 250 mL of water.

Who Is Running the Clinical Trial?

Holland Bloorview Kids Rehabilitation Hospital

Lead Sponsor

Trials

69

Recruited

14,100+

Anagnostou, Evdokia, M.D.

Lead Sponsor

Trials

3

Recruited

180+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

Ontario Brain Institute

Collaborator

Trials

12

Recruited

3,000+

Published Research Related to This Trial

In a double-blind crossover study involving 30 girls with Rett syndrome, mecasermin (rhIGF-1) did not show significant improvement in symptoms compared to placebo, and some measures indicated worsening of symptoms.

While the treatment was generally safe with mostly mild to moderate adverse events, serious adverse events were reported, and EEG parameters also showed deterioration, suggesting caution in its use for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled crossover assessment of mecasermin for the treatment of Rett syndrome. O'Leary, HM., Kaufmann, WE., Barnes, KV., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04041713?term=%22Rett+Syndrome+%22&draw=2&rank=2

A Pilot Study of an Antioxidant Cocktail vs. Placebo in the ... A type of eligibility criteria that indicates whether people who do not have the condition/disease being studied can participate in that clinical study. ... An ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9311910/

Oral Feeding of an Antioxidant Cocktail as a Therapeutic ... Here, we tested the efficacy of early targeted drug therapy using a cocktail ... Disturbances of breathing in Rett syndrome: Results from patients ...

3. withpower.com withpower.com/trial/phase-3-rett-syndrome-8-2019-f5509

Antioxidant Cocktail for Rett Syndrome · Info for Participants The antioxidant cocktail, which includes vitamin E, N-acetylcysteine, and alpha-lipoic acid, showed some benefits in mice with Rett syndrome, but long-term use ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04041713

A Pilot Study of an Antioxidant Cocktail vs. Placebo in the ... This study will examine the potential efficacy and safety of Rett-T for core motor deficits of Rett syndrome, and will explore biological markers of safety and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11486803/

Rett Syndrome: The Emerging Landscape of Treatment ... In terms of the secondary endpoints, the ADAMS scales showed meaningful improvement in 52.9% on treatment versus 8.3% on placebo (p = 0.010; ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK482252/

Rett Syndrome - StatPearls - NCBI Bookshelf Rett syndrome (RTT) is a neurodevelopmental disorder in which regression of previously acquired skills follows a period of typical development.

7. orpha.net orpha.net/en/disease/detail/778

Rett syndrome A rare severe, X-linked, neurodevelopmental disorder characterized by rapid developmental regression in infancy, partial or complete loss of purposeful hand ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06856759?cond=%22Rett%20syndrome%22&rank=5

Single-Dose AAV-MECP2 Safety/Tolerability and Efficacy ... In summary, RTT is a serious neurodevelopmental disorder that poses great harm to patients, and there is currently no effective treatment method. The clinical ...

9. bmcpediatr.biomedcentral.com bmcpediatr.biomedcentral.com/articles/10.1186/s12887-024-04526-3

Safety and efficacy of trofinetide in Rett syndrome It presents with loss of acquired skills, impaired communication, and stereotypic hand movements. Given the limited treatment options for Rett ...

10. rarediseases.org rarediseases.org/rare-diseases/rett-syndrome/

Rett Syndrome - Symptoms, Causes, Treatment | NORD However, there is an increased risk of sudden death in people with Rett syndrome. Approximately one quarter of deaths in Rett are sudden and unexpected.