Rett SyndromePhase 2NCT04041713
A Pilot Study of an Antioxidant Cocktail vs. Placebo in the Treatment of Children and Adolescents With Rett Syndrome
A Phase 2 study testing Rett-T in people with Rett Syndrome, run by Holland Bloorview Kids Rehabilitation Hospital at 1 site in Canada.
Trial summary
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 treatment response. Read more about this study
- Who is it for?
- Ages 2 to 21 years, women only
- Conditions the study is for
- Rett Syndrome
- What is being tested?
- Rett-T
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteCanada
- Study dates
- 24 Aug 2026to 30 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 21 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Female outpatients 2-21 years of age inclusive.
- Diagnosis of Rett syndrome.
- At least partially ambulatory (may need assistive device to take a step).
- If already receiving stable interventions must meet the following criteria:
- If already receiving stable concomitant medications or nutraceuticals affecting behaviour, must be on a stable dose during the preceding 1 month prior to Screening (with the exception of fluoxetine, where a period of 6 weeks is needed), and will not electively initiate new or modify ongoing medications for study duration.
- Have normal laboratory test results at Screening/Baseline. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigator.
- Ability to complete assessments, fluency in English (parent/legal guardian; participant, if verbal).
- Ability to obtain assent (if developmentally appropriate), as well as written informed consent from their parent(s)/legal guardian(s).
Who cannot join
- Pregnant females; sexually active females on inadequate birth control (extremely unlikely in this population).
- Have another serious medical condition that, based on Investigator judgment, might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Have evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease, not including mild common pediatric diseases in these areas that are stable (e.g. mild asthma, constipation, etc.).
- Have hypersensitivity to any components of Rett-T.
- Have one or more of the following: HIV, HBV, HCV, hemophilia (bleeding problems, recent nose and brain injuries), drug abuse, immunity disorder, major depressive episode or psychosis.
- Unable to tolerate venipuncture procedures for blood sampling.
- Receiving concomitant medications/nutraceuticals that include any of the components of Rett-T.
- Actively enrolled in another intervention study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Holland Bloorview Kids Rehabilitation Hospital
Toronto, Ontario, M4G 1R8
Faiza Khawaja, 4164256220 ext. 3526, fkhawaja@hollandbloorview.ca
Evdokia Anagnostou, MD
About this study
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 treatment response.
Read the detailed description
There are currently no available medicines shown to be effective for Rett syndrome. Numerous studies implicate mitochondrial dysfunction and oxidative stresses in the pathophysiology of Rett syndrome. Mitochondrial dysfunction has been reported in Rett patients, Rett mouse models and MECP2-deficient cells.
Collaborators have tested a combination of specific antioxidants known to enhance mitochondrial function in a cell and mouse model of Rett syndrome. The formulation normalized mitochondrial membrane potential in MECP2 neurons, and MECP2-deficient mice displayed improved exploratory, locomotor and social behavior compared to MECP2-deficient mice. These results support testing anti-oxidative strategies for benefit in individuals with Rett syndrome.In this study, the formulation has been adjusted and optimized based on current guidelines for human use, with the goal of translating a potential new treatment from the animal model to use in humans. Results of this study could lead to the first approved medication treatment for the disorder.
- Conditions
- Rett Syndrome
- Being tested
- Rett-T, Placebo
- Keywords
- Rett Syndrome, Rett, RTT
- Medical subject headings
- Rett Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rett-TDrug
antioxidant cocktail
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Rett T | Active comparator | 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. Receives: Drug: Rett-T |
| Placebo | Placebo comparator | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rett Syndrome Natural History Motor Behavior Assessment (MBA)
To examine the effect of Rett-T vs. placebo on measures of motor function. The Rett Syndrome MBA consists of 37 items grouped into three subscales (Behavioral/Social Assessment, Orofacial Respiratory Assessment, and Motor Assessment/Physical Signs). Items are captured on a 0-4 point Likert scale. Total and subscale scores are calculated (subscales are summed for a total score). The scale range for Total score is 0-136; for Behavioral/Social subscale, 0-60; for Orofacial/Respiratory subscale, 0-28; for Motor Assesment/Physical Signs, 0-48. For both total and subscale scores, higher values represent a worse outcome.
Measured: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
Secondary outcomes (7)
Rett Syndrome Gross Motor Scale (RSGMS)
To examine the effect of Rett-T vs. placebo on measures of motor function. The RSGMS consists of 15 gross motor items grouped into three subscales (Sitting, Standing and Walking, and Challenge). Items are captured on a 0-3 Likert Scale rating regarding level of assistance needed (0=maximal, 3 = none). Total and subscale scores are calculated (subscales are summed for a total score). The scale range for Total score is 0-45; for Sitting, 0-9; for Walking, 0-27; for Challenge, 0-9. For both total and subscale scores, higher values represent a better outcome.
Measured: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
Safety Monitoring Uniform Report Form (SMURF)
To examine the safety and tolerability of Rett- T in children and youth with Rett syndrome; To explore the effect Rett-T vs. placebo on maladaptive behaviors, anxiety, sleep, seizure
Measured: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
Clinical Global Impressions - Improvement Scale - Global (CGI-I)
To explore the effect of Rett-T vs. placebo on global improvement. The CGI-I measures global clinical improvement in response to treatment. A single score is assigned on a 1-7 Likert scale, with 1= very much improved-7=very much worse. Higher values represent a worse outcome.
Measured: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
The Top 3 Causes for Concern
To explore the effect Rett-T vs. placebo on maladaptive behaviors, anxiety, sleep, seizure frequency, and global improvement. Respondents are instructed to choose their top three concerns for the participant, and indicate Concern Number #1, 2 and 3 on the form. Respondents are next instructed to place a vertical mark along a visual analogue scale (a 10 centimetre horizontal line in which the leftmost point on the scale indicates the concern is completely absent, and the rightmost point on the scale indicates that the concern is very severe). For each concern, a measurement is taken from the leftmost point of the scale to the vertical mark, and the measurement in centimetres acts as the score. Higher scores represent a worse outcome.
Measured: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
The Rett Syndrome Behaviour Questionnaire (RSBQ)
To explore the effect of Rett-T vs. placebo on maladaptive behaviors, anxiety, sleep, seizure frequency, and global improvement. The measure consists of 45 items which are grouped into 8 subscales (General Mood, Breathing Problems, Body Rocking and Expressionless Face, Hand Behaviors, Repetitive Face Movements, Night-time Behaviors, Fear/Anxiety, and Walking/Standing). Items are measured on a 0-2 Likert scale.Total and subscale scores are calculated (subscales are summed for a total score). The scale range for total score is 0-90; for General Mood, 0-16; for Breathing Problems, 0-10; for Body Rocking and Expressionless Face, 0-12; for Hand Behaviours, 0-12; for Repetitive Face Movements, 0-8; for Nighttime Behaviours, 0-6; for Fear/Anxiety; 0-8; for Walking/Standing, 0-4. Seven items are not included in the subscale scores but are included in the total score sum. For both total and subscale scores, higher values represent a worse outcome.
Measured: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
Anxiety, Depression, and Mood Scale (ADAMS)
To explore the effect of Rett-T vs. placebo on anxiety. The ADAMS consists of 28 items grouped into five subscales (Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, and Obsessive Behavior). Items are scored on a 0-3 Likert scale that combines frequency and severity ratings (where 0=behavior has not occurred or is not a problem, 3=behavior occurs a lot or is a severe problem). Each subscale score is calculated separately; the scale range for Manic/Hyperactive Behavior is 3-15; for Depressed Mood, 7-21; for Social Avoidance, 7-21; for General Anxiety, 7-21; for Obsessive Behavior, 3-9. For each subscale score, higher values represent a worse outcome.
Measured: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
Children's Sleep Habits Questionnaire (CSHQ)
To explore the effect of Rett-T vs. placebo on sleep. The CSHQ is a tool designed to screen for the most common sleep problems in children. The CSHQ consists of 35 items for scoring and extra unscored items intended to provide administrators with other potentially useful information about respondents. The instrument evaluates sleep based on behavior within eight different subscales (Bedtime Resistance, Sleep-Onset Delay, Sleep Duration, Sleep Anxiety, Night Wakings, Parasomnias, Sleep-Disordered Breathing, and Daytime Sleepiness).Total and subscale scores are calculated (33 items are summed for a total score). The scale range for Total score is 33-99; for Bedtime Resistance subscale, 6-18; for Sleep Onset/Delay, 1-3; for Sleep Duration, 3-9; for Sleep Anxiety, 4-12; For Night Wakings, 3-9; for Parasomnias, 7-21; for Sleep-Disordered Breathing, 3-9; for Daytime Sleepiness, 8-24. For both total and subscale scores, higher values represent a worse outcome.
Measured: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2019
- Study start24 Aug 2026 (estimated)
- Primary completion30 Dec 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This is an 18-week pilot, single site, randomized,double blind, placebo-controlled cross-over trial of Rett-T vs. placebo. Periods I and II of the randomized study are 8 weeks long with a 2 week washout period.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Holland Bloorview Kids Rehabilitation Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ontario Brain Institute, Unity Health Toronto
- Responsible party
- Sponsor
- Investigators
- Evdokia Anagnostou, MD, Principal investigator, Holland Bloorview Kids Rehabilitation Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04041713
- Sponsor's protocol ID
- RETT-08-2018
- Status last verified
- Jul 2026
- First submitted
- 27 Jun 2019
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of an Antioxidant Cocktail vs. Placebo in the Treatment of Children and Adolescents With Rett Syndrome
- ClinicalTrials.gov ID
- NCT04041713
- Acronym / sponsor ID
- RETT-08-2018
- Conditions
- Rett Syndrome
- Keywords
- Rett Syndrome, Rett, RTT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Holland Bloorview Kids Rehabilitation HospitalUniversity, hospital or other
- Collaborators
- Ontario Brain Institute, Unity Health Toronto
- Study start
- 24 Aug 2026 (estimated)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 1 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 treatment response.
Detailed description
There are currently no available medicines shown to be effective for Rett syndrome. Numerous studies implicate mitochondrial dysfunction and oxidative stresses in the pathophysiology of Rett syndrome. Mitochondrial dysfunction has been reported in Rett patients, Rett mouse models and MECP2-deficient cells.
Collaborators have tested a combination of specific antioxidants known to enhance mitochondrial function in a cell and mouse model of Rett syndrome. The formulation normalized mitochondrial membrane potential in MECP2 neurons, and MECP2-deficient mice displayed improved exploratory, locomotor and social behavior compared to MECP2-deficient mice. These results support testing anti-oxidative strategies for benefit in individuals with Rett syndrome.In this study, the formulation has been adjusted and optimized based on current guidelines for human use, with the goal of translating a potential new treatment from the animal model to use in humans. Results of this study could lead to the first approved medication treatment for the disorder.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is an 18-week pilot, single site, randomized,double blind, placebo-controlled cross-over trial of Rett-T vs. placebo. Periods I and II of the randomized study are 8 weeks long with a 2 week washout period.
| Arm | Type | Receives |
|---|---|---|
| Rett T | Active comparator | Drug: Rett-TRett 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. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo 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 may qualify
- Ages
- 2 to 21 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Female outpatients 2-21 years of age inclusive.
- Diagnosis of Rett syndrome.
- At least partially ambulatory (may need assistive device to take a step).
- If already receiving stable interventions must meet the following criteria:
- Have normal laboratory test results at Screening/Baseline. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigator.
Key exclusion criteria (7 listed)
- Pregnant females; sexually active females on inadequate birth control (extremely unlikely in this population).
- Have another serious medical condition that, based on Investigator judgment, might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Have evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease, not including mild common pediatric diseases in these areas that are stable (e.g. mild asthma, constipation, etc.).
- Have hypersensitivity to any components of Rett-T.
- Have one or more of the following: HIV, HBV, HCV, hemophilia (bleeding problems, recent nose and brain injuries), drug abuse, immunity disorder, major depressive episode or psychosis.
- Unable to tolerate venipuncture procedures for blood sampling.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rett-Tantioxidant cocktail | Drug | Rett T |
| PlaceboPlacebo | Other | Placebo |
Primary outcome
Rett Syndrome Natural History Motor Behavior Assessment (MBA)
Time frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
To examine the effect of Rett-T vs. placebo on measures of motor function. The Rett Syndrome MBA consists of 37 items grouped into three subscales (Behavioral/Social Assessment, Orofacial Respiratory Assessment, and Motor Assessment/Physical Signs). Items are captured on a 0-4 point Likert scale. Total and subscale scores are calculated (subscales are summed for a total score). The scale range for Total score is 0-136; for Behavioral/Social subscale, 0-60; for Orofacial/Respiratory subscale, 0-28; for Motor Assesment/Physical Signs, 0-48. For both total and subscale scores, higher values represent a worse outcome.
7 secondary outcomes
Rett Syndrome Gross Motor Scale (RSGMS)
Time frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
Safety Monitoring Uniform Report Form (SMURF)
Time frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
Clinical Global Impressions - Improvement Scale - Global (CGI-I)
Time frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
The Top 3 Causes for Concern
Time frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
The Rett Syndrome Behaviour Questionnaire (RSBQ)
Time frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
Anxiety, Depression, and Mood Scale (ADAMS)
Time frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
Children's Sleep Habits Questionnaire (CSHQ)
Time frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Evdokia Anagnostou, MD principal investigator
Holland Bloorview Kids Rehabilitation Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rett-T in people with Rett Syndrome, run by Holland Bloorview Kids Rehabilitation Hospital at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Faiza Khawaja (416 425 6220 ext. 3526, fkhawaja@hollandbloorview.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rett Syndrome Natural History Motor Behavior Assessment (MBA) (time frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.