Double-blind Placebo Controlled Study of Oxytocin in Fragile X Syndrome

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01254045
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 6
• Duration (Months): 35
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fragile X Syndrome	Drug: placebo; Drug: oxytocin 24IU; Drug: oxytocin 48IU	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Double-blind Placebo Controlled Study of Oxytocin in Fragile X Syndrome
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: placebo, oxytocin 24IU, oxytocin 48IU intranasal placebo (48 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (24 international units; 4IU per puff) and intranasal placebo (24 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (48 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles	Drug: placebo; intranasal placebo (48 international units); Drug: oxytocin 24IU; intranasal oxytocin (24 international units) and intranasal placebo (24 international units); Other Names: Syntocinon ; Drug: oxytocin 48IU; intranasal oxytocin (48 international units); Other Names: Syntocinon
Experimental: oxytocin 24IU, placebo, oxytocin 48IU intranasal oxytocin (24 international units; 4IU per puff) and intranasal placebo (24 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal placebo (48 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (48 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles	Drug: placebo; intranasal placebo (48 international units); Drug: oxytocin 24IU; intranasal oxytocin (24 international units) and intranasal placebo (24 international units); Other Names: Syntocinon ; Drug: oxytocin 48IU; intranasal oxytocin (48 international units); Other Names: Syntocinon
Experimental: oxytocin 48IU, oxytocin 24IU, placebo intranasal oxytocin (48 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (24 international units; 4IU per puff) and intranasal placebo (24 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal placebo (48 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles	Drug: placebo; intranasal placebo (48 international units); Drug: oxytocin 24IU; intranasal oxytocin (24 international units) and intranasal placebo (24 international units); Other Names: Syntocinon ; Drug: oxytocin 48IU; intranasal oxytocin (48 international units); Other Names: Syntocinon
Experimental: oxytocin 24IU, oxytocin 48IU, placebo intranasal oxytocin (24 international units; 4IU per puff) and intranasal placebo (24 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (48 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal placebo (48 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles	Drug: placebo; intranasal placebo (48 international units); Drug: oxytocin 24IU; intranasal oxytocin (24 international units) and intranasal placebo (24 international units); Other Names: Syntocinon ; Drug: oxytocin 48IU; intranasal oxytocin (48 international units); Other Names: Syntocinon
Experimental: oxytocin 48IU, placebo, oxytocin 24IU intranasal oxytocin (48 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal placebo (48 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles ; intranasal oxytocin (24 international units) and intranasal placebo (24 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles	Drug: placebo; intranasal placebo (48 international units); Drug: oxytocin 24IU; intranasal oxytocin (24 international units) and intranasal placebo (24 international units); Other Names: Syntocinon ; Drug: oxytocin 48IU; intranasal oxytocin (48 international units); Other Names: Syntocinon
Experimental: placebo, oxytocin 48IU, oxytocin 24IU intranasal placebo (48 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (48 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (24 international units; 4IU per puff) and intranasal placebo (24 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles	Drug: placebo; intranasal placebo (48 international units); Drug: oxytocin 24IU; intranasal oxytocin (24 international units) and intranasal placebo (24 international units); Other Names: Syntocinon ; Drug: oxytocin 48IU; intranasal oxytocin (48 international units); Other Names: Syntocinon

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 29 Years
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Allan L Reiss, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allan Reiss, Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT01254045
• Other Study ID Numbers: SU-11182010-7215; 8618
• First Posted: Dec 6, 2010
• Last Update Posted: Mar 18, 2020
• Last Verified: Mar 1, 2020

• Additional relevant MeSH terms: Fragile X Syndrome; Syndrome; Oxytocin

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Placebo 48IU, Oxytocin 24IU/Placebo 24IU, Oxytocin 48IU	Oxytocin 24IU/Placebo 24IU, Placebo 48IU, Oxytocin 48IU	Oxytocin 48IU, Oxytocin 24IU/Placebo 24IU, Placebo 48IU	Oxytocin 24IU/Placebo 24IU, Oxytocin 48IU, Placebo 48IU	Oxytocin 48IU, Placebo 48IU, Oxytocin 24IU/Placebo 24IU	Placebo 48IU, Oxytocin 48IU, Oxytocin 24IU/Placebo 24IU
Arm/Group Description	intranasal placebo (48 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (24 international units; 4IU per puff) and placebo (24 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (48 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles	intranasal oxytocin (24 international units; 4IU per puff) and intranasal placebo (24 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal placebo (48 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (48 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles	intranasal oxytocin (48 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (24 international units; 4IU per puff) and intranasal placebo (24 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal placebo (48 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles	intranasal oxytocin (24 international units; 4IU per puff) and intranasal placebo (24 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (48 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal placebo (48 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles	intranasal oxytocin (48 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal placebo (48 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles ; intranasal oxytocin (24 international units; 4IU per puff) and intranasal placebo (24 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles	intranasal placebo (48 international units; 4IU per puff) once at baseline, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (48 international units; 4IU per puff) once at time 2, 6 puffs (3 puffs per nostril) from each of 2 bottles; intranasal oxytocin (24 international units; 4IU per puff) and intranasal placebo (24 international units; 4IU per puff) once at time 3, 6 puffs (3 puffs per nostril) from each of 2 bottles
Period Title: First/Baseline (1 Day at Week 1 )
STARTED	2	2	2	1	1	1
COMPLETED	1	2	2	1	1	1
NOT COMPLETED	1	0	0	0	0	0
Period Title: First/Baseline (1 Day at Week 1 )
STARTED	1	2	2	1	1	1
COMPLETED	1	2	2	1	1	1
NOT COMPLETED	0	0	0	0	0	0
Period Title: First/Baseline (1 Day at Week 1 )
STARTED	1	2	2	1	1	1
COMPLETED	1	2	2	1	1	1
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Includes groups randomized to one of six different sequences of three interventions (placebo, oxytocin 24IU, oxytocin 48IU).
Overall Participants	9
Age (Count of Participants)
<=18 years	2 22.2%
Between 18 and 65 years	7 77.8%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.89 (4.73)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	9 100%
Region of Enrollment (participants) [Number]
United States	9 100%

Outcome Measures

1. Primary Outcome

Title	Eye Contact/Gaze During 10 Minute Social Challenge Task
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Oxytocin 24IU/Placebo 24IU	48IU OT
Arm/Group Description	placebo (48IU)	24 international units of intranasal oxytocin and 24 international units of placebo	48 international units of intranasal oxytocin
Measure Participants	8	8	8
Mean (Standard Error) [eye contact/gaze events per 10 minutes]	15.4 (3.5)	20.9 (3.6)	17.0 (4.5)

2. Secondary Outcome

Title	Salivary Cortisol
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	24IU OT	48IU OT
Arm/Group Description	placebo (48 IU)	24 international units of intranasal oxytocin and 24 IU of placebo	48 international units of intranasal oxytocin
Measure Participants	8	8	8
Mean (Standard Error) [nmol/L]	6.33 (.86)	4.67 (.56)	4.37 (.92)

Adverse Events

Arm/Group Title	Intervention: Placebo 48IU		Intervention: Oxytocin 24IU/Placebo 24IU		Intervention: Oxytocin 48IU
Arm/Group Description	Two participants received placebo 48IU at baseline. Three participants received placebo 48IU at Time 2. Three participants received placebo 48IU at Time 3. This study is a cross-over design.		Three participants received Oxytocin 24IU/Placebo 24IU at baseline. Three participants received Oxytocin 24IU/Placebo 24IU at Time 2. Two participants received Oxytocin 24IU/Placebo 24IU at Time 3. This study is a cross-over design.		Three participants received Oxytocin 48IU at baseline. Two participants received Oxytocin 48IU at Time 2. Three participants received Oxytocin 48IU at Time 3. This study is a cross-over design.
All Cause Mortality
	Intervention: Placebo 48IU		Intervention: Oxytocin 24IU/Placebo 24IU		Intervention: Oxytocin 48IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Intervention: Placebo 48IU		Intervention: Oxytocin 24IU/Placebo 24IU		Intervention: Oxytocin 48IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Intervention: Placebo 48IU		Intervention: Oxytocin 24IU/Placebo 24IU		Intervention: Oxytocin 48IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		1/8 (12.5%)		0/8 (0%)
Nervous system disorders
Bell's palsy	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.