A Phase 1/2 interventional study of Ketamine in ADNP Syndrome, sponsored by Alexander Kolevzon. Completed at 1 site in United States. Open to participants aged 5 Years to 12 Years. Per ClinicalTrials.gov, last updated 2023-07-07.
Sponsored by Alexander Kolevzon · Phase 1/2, Interventional, and Treatment
This is a Phase 2A, single dose, open-label study to evaluate the safety, tolerability, and efficacy of a low-dose, 40-minute infusion into the veins (intravenous infusion or "IV") of ketamine in children with ADNP syndrome (Activity-Dependent Neuroprotective Protein). The study team will enroll 10 participants, ages 5 to 12, at Mount Sinai. The study participation is expected to last 4 weeks and will include 5 scheduled clinic visits in order to complete safety monitoring, clinical assessments, and biomarker collection. At the conclusion of this study, the study team expects to demonstrate the safety and tolerability of low-dose ketamine in children with ADNP syndrome. Additionally, the study team anticipates identifying meaningful signals of efficacy in clinical outcome measures using RNA and DNA sequencing to analyze ADNP protein expression and DNA methylation profiles, a natural process by which methyl groups are added to the DNA to change its activity, in order to assess sensitivity to change with low-dose ketamine treatment and inform future phase 3 studies. Ketamine is not currently approved by the Food and Drug Administration to treat this syndrome, but it is approved for use in children in other situations, for example in anesthesia.
13 studies on the registry are indexed under Chromosome Disorders; 4 are open to participants now.
Browse Chromosome Disorders studies →Alexander Kolevzon is the lead sponsor of 4 studies on the registry; none are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Total dose administration or 0.5 mg/kg of ketamine
Drug: Ketamine
A single 40-minute intravenous infusion
Number of Participants With an Adverse Event
Number of Participants with an adverse event as defined by the Systematic Longitudinal Assessment of Adverse Events (SLAES) which is a comprehensive form that assesses medical and behavioral conditions that were present at screening and/or baseline. Conditions are considered treatment emergent if their severity increased significantly after the participant had taken at least one dose of the study treatment. Treatment emergent adverse events will be tracked considered in the adverse event safety analysis. Severity of adverse events are categorized as mild, moderate, severe, life-threatening, or resulting in death and the treating physician indicates if the adverse event was related or unrelated to study drug.
Time frame: Week 4
Aberrant Behavior Checklist
Changes in scale at week 1 compared to baseline. Aberrant Behavior Checklist is a behavior rating scale for the assessment of treatment effects. Each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). Subscales from 0-45 for Irritability; 0-48 for Social Withdrawal and Hyperactivity; from 0-21 for Stereotypy; and 0-12 for In Speech , with total scale from 0 to 48, with higher score indicating worse health outcomes.
Time frame: Baseline, Week 1
Anxiety, Depression and Mood Scales (ADAMS)
The ADAMS is a parent/caregiver-completed measure and consists of 28 items, grouped into five subscales (Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, Obsessive Behavior), and scored on a four-point Likert scale that combines frequency and severity ratings from 0-3. Subscales range - Hyperactivity 0-15; Depressed 0-21; Social Avoidance 0-21; General anxiety 0-21; OCD 0-9. Scores are not summed. Higher score indicates poorer health outcomes.
Time frame: Baseline and Week 1
Repetitive Behavior Scale-Revised (RBS-R)
Change in repetitive behaviors at weeks 1 compared to baseline. RBS-R subscales - Stereo 0-18; Self injury 0-24; Compulsive 0-24; Ritualistic 0-18; Sameness 0-33; Restricted 0-12. Total scale range from 0 to 126 with higher score indicating worse health outcomes.
Time frame: Baseline, Week 1
Clinical Global Impressions - Improvement Scale (CGI-I)
Changes in scale at weeks 2, and 4 compared to baseline. Clinical Global impressions - Improvement Scale is anchored to symptoms of ADNP syndrome for the assessment of treatment effects. CGI-I total score from 1 to 7 point scale, with higher score indicating worse health outcomes.
Time frame: Baseline, Week 2, and Week 4
Childrens Sleep Habits Questionnaire
Change in sleep habits at week 1 compared to baseline. Full scale from 0 to 110, with higher score indicating worse health outcomes.
Time frame: Baseline, Week 1
Peabody Picture Vocabulary Test and Expressive Vocabulary Test
Expressive and receptive language assessed by Peabody Picture Vocabulary Test and Expressive Vocabulary Test at Day 1, Weeks 1, 2, and 4. Full scale from 40 to 160, with higher score indicating better health outcomes.
Time frame: Baseline, Week 1, Week 2, and Week 4
Proportion of Target-First Trials Saccades
Change at Day 1 and Week 1 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see a video of a person with two objects, turning her head towards one of the objects, the target. Mean proportion of trials in which participants made saccades to the target before the distractor.
Time frame: Baseline, Day 1, Week 1
Latency to First Saccade
Change at week 1, week 2, and week 4 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see different social and non-social stimuli. Latency to first saccade to the target
Time frame: Baseline, Day 1, Week 1
Proportion of Target-Dwelling
Change at Day 1 and Week 1 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see different social and non-social stimuli. Proportion of time participants spent dwelling on the target versus distractor.
Time frame: Baseline, Day 1, Week 1
Electrophysiology Recording
Electroencephalographic recordings to measure Auditory Event Related Potentials at baseline, week 1, week 2, and week 4. In separate blocks, participants heard a 500-ms click at either a stimulation rate of 40 or 20 Hz. Click trains were presented 150 times each, with an intertrial interval of 50 ms, at approximately 60 db. Higher number indicates higher amplitude neural response to auditory stimuli.
Time frame: Baseline, Week 1, Week 2, and Week 4
Vineland Adaptive Behavior Scales
Changes in scale at week 4 compared to baseline. Vineland Adaptive Behavior Scales measures adaptive functioning. Higher score indicating better health outcomes. Domain scores are standard scores - population mean 100 standard deviation 15. an overall composite score, it consists of three subscales: (a) communication (receptive, expressive, written), (b) socialization (interpersonal relationships, play and leisure, coping skills), and (c) daily living (person, domestic, community).
Time frame: Baseline and Week 4
Caregiver Strain Questionnaire (CGSQ)
Caregiver Strain Questionnaire (CGSQ) is a 13 question tool, with a 5-point Likert scale ranging from Not at all (0) to Very much (4). Domains (Objective strain, Subjective externalized strain, Subjective internalized strain) are averaged scores, range from 0-4. Total score (Global score) is a sum of the three subdomains. Full scale range 0-12, higher score indicates more severe strain.
Time frame: Baseline and Week 1
Ten participants were screened, and all met criteria for inclusion and were enrolled between August 2020 and May 2021.
| Milestone | Ketamine |
|---|---|
| Started | 10 |
| Completed | 10 |
| Not completed | 0 |
Number of Participants with an adverse event as defined by the Systematic Longitudinal Assessment of Adverse Events (SLAES) which is a comprehensive form that assesses medical and behavioral conditions that were present at screening and/or baseline. Conditions are considered treatment emergent if their severity increased significantly after the participant had taken at least one dose of the study treatment. Treatment emergent adverse events will be tracked considered in the adverse event safety analysis. Severity of adverse events are categorized as mild, moderate, severe, life-threatening, or resulting in death and the treating physician indicates if the adverse event was related or unrelated to study drug.
| Participants | Ketamine |
|---|---|
| Number of Participants With an Adverse Event | 9 |
Changes in scale at week 1 compared to baseline. Aberrant Behavior Checklist is a behavior rating scale for the assessment of treatment effects. Each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). Subscales from 0-45 for Irritability; 0-48 for Social Withdrawal and Hyperactivity; from 0-21 for Stereotypy; and 0-12 for In Speech , with total scale from 0 to 48, with higher score indicating worse health outcomes.
| score on a scale | Caregiver Rated Assessment at Baseline | Caregiver Rated Assessment at 1 Week |
|---|---|---|
| Irritability | 20.5 ± 13.33 | 10.9 ± 10.6 |
| Social withdrawal | 9.9 ± 8.96 | 4.2 ± 4.96 |
| Motor stereotypies | 7.8 ± 5.31 | 4.5 ± 3.66 |
| Hyperactivity | 24.5 ± 14.66 | 16.2 ± 13.35 |
| Inappropriate speech | 3.6 ± 2.88 | 3.3 ± 2.21 |
The ADAMS is a parent/caregiver-completed measure and consists of 28 items, grouped into five subscales (Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, Obsessive Behavior), and scored on a four-point Likert scale that combines frequency and severity ratings from 0-3. Subscales range - Hyperactivity 0-15; Depressed 0-21; Social Avoidance 0-21; General anxiety 0-21; OCD 0-9. Scores are not summed. Higher score indicates poorer health outcomes.
| score on a scale | Caregiver Rated Assessment at Baseline | Caregiver Rated Assessment Week 1 |
|---|---|---|
| Hyperactivity | 10.1 ± 4.23 | 6.7 ± 3.5 |
| Depressed | 2.6 ± 3.31 | 2.1 ± 2.69 |
| Social avoidance | 6.1 ± 4.23 | 3.5 ± 3.47 |
| General anxiety | 6.3 ± 5.96 | 4.3 ± 4.74 |
| Obsessive/compulsive | 2.5 ± 2.01 | 1.6 ± 1.51 |
Change in repetitive behaviors at weeks 1 compared to baseline. RBS-R subscales - Stereo 0-18; Self injury 0-24; Compulsive 0-24; Ritualistic 0-18; Sameness 0-33; Restricted 0-12. Total scale range from 0 to 126 with higher score indicating worse health outcomes.
| score on a scale | Caregiver Rated Assessment at Baseline | Caregiver Rated Assessment at 1 Week |
|---|---|---|
| Stereotyped | 6.6 ± 3.31 | 5.1 ± 4.93 |
| Self-injury | 5.9 ± 4.79 | 4.2 ± 3.49 |
| Compulsive | 3.7 ± 2.75 | 2.2 ± 1.87 |
| Ritualistic | 2.9 ± 3.63 | 2.9 ± 2.38 |
| Sameness | 5.6 ± 6.33 | 4.3 ± 5.46 |
| Restricted | 3.9 ± 3.14 | 3.6 ± 2.37 |
| Overall | 28.6 ± 17.56 | 22.3 ± 14.28 |
Changes in scale at weeks 2, and 4 compared to baseline. Clinical Global impressions - Improvement Scale is anchored to symptoms of ADNP syndrome for the assessment of treatment effects. CGI-I total score from 1 to 7 point scale, with higher score indicating worse health outcomes.
| score on a scale | Ketamine |
|---|---|
| Baseline | 0 ± 0 |
| Week 2 | 1.5 ± 0.53 |
| Week 4 | 1.0 ± 0.52 |
Change in sleep habits at week 1 compared to baseline. Full scale from 0 to 110, with higher score indicating worse health outcomes.
| units on a scale | Caregiver Rated Assessment at Baseline | Caregiver Rated Assessment at 1 Week |
|---|---|---|
| Childrens Sleep Habits Questionnaire | 2.83 ± 0.75 | 2.93 ± 0.82 |
Expressive and receptive language assessed by Peabody Picture Vocabulary Test and Expressive Vocabulary Test at Day 1, Weeks 1, 2, and 4. Full scale from 40 to 160, with higher score indicating better health outcomes.
| score on a scale | Ketamine |
|---|---|
| Baseline, Day 1 | 50.9 ± 13.40 |
| Week 1 | 52.8 ± 17.38 |
| Week 2 | 51.5 ± 13.87 |
| Week 4 | 50.9 ± 15.29 |
Change at Day 1 and Week 1 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see a video of a person with two objects, turning her head towards one of the objects, the target. Mean proportion of trials in which participants made saccades to the target before the distractor.
| proportion of target-first saccades | Ketamine |
|---|---|
| Baseline | 0.53 ± 0.14 |
| Day 1 | 0.75 ± 0.17 |
| Week 1 | 0.70 ± 0.14 |
Change at week 1, week 2, and week 4 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see different social and non-social stimuli. Latency to first saccade to the target
| ms | Ketamine |
|---|---|
| Baseline | 2319.38 ± 1202.34 |
| Day 1 | 2089.96 ± 754.70 |
| Week 1 | 1674.18 ± 301.93 |
Change at Day 1 and Week 1 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see different social and non-social stimuli. Proportion of time participants spent dwelling on the target versus distractor.
| proportion of time | Ketamine |
|---|---|
| Baseline | 0.51 ± 0.19 |
| Day 1 | 0.59 ± 0.13 |
| Week 1 | 0.66 ± 0.11 |
Electroencephalographic recordings to measure Auditory Event Related Potentials at baseline, week 1, week 2, and week 4. In separate blocks, participants heard a 500-ms click at either a stimulation rate of 40 or 20 Hz. Click trains were presented 150 times each, with an intertrial interval of 50 ms, at approximately 60 db. Higher number indicates higher amplitude neural response to auditory stimuli.
| ms | Ketamine |
|---|---|
| 20-Hz Baseline | 0.18 ± 0.06 |
| 20-Hz Week 1 | 0.15 ± 0.05 |
| 20-Hz Week 2 | 0.18 ± 0.06 |
| 20-Hz Week 4 | 0.19 ± 0.11 |
| 40-Hz Baseline | 0.19 ± 0.03 |
| 40-Hz Week1 | 0.26 ± 0.09 |
| 40-Hz Week 2 | 0.18 ± 0.06 |
| 40-Hz Week 4 | 0.20 ± 0.06 |
Changes in scale at week 4 compared to baseline. Vineland Adaptive Behavior Scales measures adaptive functioning. Higher score indicating better health outcomes. Domain scores are standard scores - population mean 100 standard deviation 15. an overall composite score, it consists of three subscales: (a) communication (receptive, expressive, written), (b) socialization (interpersonal relationships, play and leisure, coping skills), and (c) daily living (person, domestic, community).
| score on a scale | Caregiver Rated Assessment at Baseline | Caregiver Rated Assessment at Week 4 |
|---|---|---|
| Abc | 42.7 ± 13.9 | 44.0 ± 15.19 |
| Comm | 32.6 ± 14.73 | 33.4 ± 15.53 |
| Daily Living | 48.5 ± 14.45 | 49.2 ± 16.14 |
| Social | 44.5 ± 15.62 | 46.8 ± 16.90 |
| Motor | 51.5 ± 8.73 | 49.83 ± 4.58 |
Caregiver Strain Questionnaire (CGSQ) is a 13 question tool, with a 5-point Likert scale ranging from Not at all (0) to Very much (4). Domains (Objective strain, Subjective externalized strain, Subjective internalized strain) are averaged scores, range from 0-4. Total score (Global score) is a sum of the three subdomains. Full scale range 0-12, higher score indicates more severe strain.
| score on a scale | Caregiver Rated Assessment at Baseline | Caregiver Rated Assessment at 1 Week |
|---|---|---|
| Objective strain | 2.79 ± 1.11 | 2.45 ± 0.99 |
| Subjective externalized strain | 2.18 ± 1.11 | 1.62 ± 0.69 |
| Subjective internalized strain | 3.3 ± 1.15 | 2.7 ± 0.97 |
| Global score | 8.27 ± 3.08 | 6.77 ± 2.32 |
Collected over 4 Weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ketamine | 0/10 (0%) | 0/10 (0%) | 9/10 (90%) |
| Event | Ketamine |
|---|---|
| Elated/sillyPsychiatric disorders | 5/10 |
| AggressionPsychiatric disorders | 4/10 |
| FatigueNervous system disorders | 4/10 |
| Decreased appetiteGeneral disorders | 3/10 |
| AnxietyPsychiatric disorders | 3/10 |
| Increased appetiteGeneral disorders | 2/10 |
| RestlessPsychiatric disorders | 2/10 |
| Increased fluid intakeGeneral disorders | 2/10 |
| Nausea/vomitingGastrointestinal disorders | 2/10 |
| Moody/irritablePsychiatric disorders | 2/10 |
| Age, Continuous(years) | Ketamine |
|---|---|
| Mean | 9.50 ± 2.30 |
| Sex: Female, Male(Participants) | Ketamine |
|---|---|
| Female | 3 |
| Male | 7 |
| Race/Ethnicity, Customized(Participants) | Ketamine |
|---|---|
| Hispanic/Latino | 2 |
| White | 8 |
| Developmental quotient(quotient) | Ketamine |
|---|---|
| VDQ - verbal developmental quotient | 26.71 ± 15.33 |
| NVDQ - nonverbal developmental quotient | 31.28 ± 16.13 |
| FSDQ - full scale developmental quotient | 28.81 ± 15.42 |
| Number of Participants with ASD(Participants) | Ketamine |
|---|---|
| Count of participants | 4 |
| Number of Participants with ADHD(Participants) | Ketamine |
|---|---|
| Count of participants | 7 |
| Genetic mutation(Participants) | Ketamine |
|---|---|
| Frameshift | 6 |
| Nonsense | 4 |
Plan to share: No
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Studies of the drug tested here: Ketamine
Alexander Kolevzon