Fragile X Syndrome
Conditions
Brief summary
The purpose of this study is to determine whether the medication oxytocin is an effective and tolerable treatment in adolescent males with fragile X syndrome (FraX) for improving socially appropriate behaviors and reducing social anxiety.
Detailed description
Twelve male adolescent (13-24 years) subjects with confirmed genetic diagnosis of FraX (full mutation) will participate in this randomized double-blind placebo-controlled study. They will receive a dose of either 24 IU oxytocin, 48 IU oxytocin or placebo at each of three visits to the lab, with each visit spaced one week apart. The efficacy of each dose will be evaluated using behavioral, cognitive and physiological metrics. If individual subject results suggest that either of the oxytocin dosage levels (24 IU or 48 IU) is superior to placebo in the double-blind phase, a single-blind trial using the optimal dosage of oxytocin will then be administered daily for 14 days by parents at home. Subjects will then come into the lab for a final assessment on Day 30. Determination of beneficial response to oxytocin will be based on a 20% change (improvement) in behavior or test performance (see below). If both oxytocin dosage levels provide similar benefits compared to placebo, the lower dose will be chosen for the 14 day single-blind trial.
Interventions
DRUGplacebo
intranasal placebo (48 international units)
DRUGoxytocin 24IU
intranasal oxytocin (24 international units) and intranasal placebo (24 international units)
DRUGoxytocin 48IU
intranasal oxytocin (48 international units)
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
13 Years to 29 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed genetic diagnosis of Fragile X (FraX) (full mutation). 2. Male (who have more serious effects due to the X chromosome nature of the disorder) 3. Age 13-29 years. 4. Parent of adolescent must be willing to sign informed consent. 5. Intelligence Quotient (IQ) \> 42.
Exclusion criteria
1. Cardiac risk factors. 2. Medication exclusions: opiates or opiate antagonists, corticosteroids, typical or atypical antipsychotics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Eye Contact/Gaze During 10 Minute Social Challenge Task | baseline, week 2, and week 3 | Number of times that eye gaze occurred (i.e., participant looked at female experimenter in the eyes) during 10 minute social challenge task (first 5 minutes social proximity, second 5 minutes social interaction). The social challenge task occurred 50 minutes after internasal dose (of placebo, placebo + oxytocin, or oxytocin) at baseline, week 2, and week 3 visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Salivary Cortisol | baseline, week 2, and week 3 | salivary cortisol level measured immediately before social challenge task and 20 minutes following social challenge task at each time point (i.e., baseline, week 2, and week 3) |
Countries
United States
Participant flow
Pre-assignment details
Ten enrolled. One on antipsychotic mediation at baseline excluded, and one lost to follow-up after baseline. Eight participants included in data analysis. Each participant received a dose of either oxytocin(OT) 24 international units (IU)/intranasal placebo 24IU, OT 48IU, or placebo 48IU at each of 3 weekly visits.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Includes groups randomized to one of six different sequences of three interventions (placebo, oxytocin 24IU, oxytocin 48IU). | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First/Baseline (1 Day at Week 1 ) | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 2 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 20.89 years STANDARD_DEVIATION 4.73 |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 1 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Eye Contact/Gaze During 10 Minute Social Challenge Task
Number of times that eye gaze occurred (i.e., participant looked at female experimenter in the eyes) during 10 minute social challenge task (first 5 minutes social proximity, second 5 minutes social interaction). The social challenge task occurred 50 minutes after internasal dose (of placebo, placebo + oxytocin, or oxytocin) at baseline, week 2, and week 3 visits.
Time frame: baseline, week 2, and week 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Eye Contact/Gaze During 10 Minute Social Challenge Task | 15.4 eye contact/gaze events per 10 minutes | Standard Error 3.5 |
| Oxytocin 24IU/Placebo 24IU | Eye Contact/Gaze During 10 Minute Social Challenge Task | 20.9 eye contact/gaze events per 10 minutes | Standard Error 3.6 |
| 48IU OT | Eye Contact/Gaze During 10 Minute Social Challenge Task | 17.0 eye contact/gaze events per 10 minutes | Standard Error 4.5 |
Secondary
Salivary Cortisol
salivary cortisol level measured immediately before social challenge task and 20 minutes following social challenge task at each time point (i.e., baseline, week 2, and week 3)
Time frame: baseline, week 2, and week 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Salivary Cortisol | 6.33 nmol/L | Standard Error 0.86 |
| Oxytocin 24IU/Placebo 24IU | Salivary Cortisol | 4.67 nmol/L | Standard Error 0.56 |
| 48IU OT | Salivary Cortisol | 4.37 nmol/L | Standard Error 0.92 |