PET Imaging of mGLuR5 With Drug Challenge

• ClinicalTrials.gov Identifier: NCT01691092
• Recruitment Status: Completed
• First Posted: September 24, 2012
• Results First Posted: April 21, 2017
• Last Update Posted: April 21, 2017
• Sponsor: Yale University
• Information provided by (Responsible Party): Yale University

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other
• Conditions: Major Depressive Disorder; Post-Traumatic Stress Disorder (PTSD)
• Intervention: Drug: Ketamine
• Enrollment: 79

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Ketamine
Arm/Group Description	All subjects will receive ketamine Ketamine: All subjects will receive ketamine to induce glutamate release in the brain
Period Title: Overall Study
Started	79
Completed	38
Not Completed	41
Reason Not Completed
Lost to Follow-up	10
Physician Decision	4
Withdrawal by Subject	3
non-compliance	3
used for different study	2
screen fail	19

Baseline Characteristics

Arm/Group Title		Ketamine
Arm/Group Description		All subjects will receive ketamine Ketamine: All subjects will receive ketamine to induce glutamate release in the brain
Overall Number of Baseline Participants		42
Baseline Analysis Population Description		reason for discrepancy: some subjects completed baseline scan but did not continue with ketamine administration and subsequent scans.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	42 participants
		34.07143 (12.12615)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants
	Female	28 66.7%
	Male	14 33.3%
diagnosis; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants
	Healthy Control (HC)	20 47.6%
	Major Depressive Disorder (MDD)	14 33.3%
	Post-Traumatic Stress Disorder (PTSD)	4 9.5%
	Comorbid MDD & PTSD	4 9.5%

Outcome Measures

1. Primary Outcome

Title	Change in Glutamate Levels at Baseline and After Ketamine Administration as Confirmed by Positron Emission Tomography (PET) Imaging
Description	PET imaging obtained in healthy and Major Depressive Disorder (MDD) subjects. Glutamate levels determined by radiotracer uptake in PET images.
Time Frame	1st scan: 90 minute baseline scan; 2nd scan: 90 minutes, ketamine administration at start of scan; scan 3: 90 minute scan 24 hours post ketamine

Outcome Measure Data

Analysis Population Description

13 healthy (6 males, 7 females) and 14 MDD non-smokers (4 males, 10 females) Mean age: 33.5 ± 13.2 yrs reasons for discrepancy (participant flow module): some data was not able to be analyzed due to elevated metabolites; some subject did not tolerate ketamine and had to be pulled out of scanner so we could not obtain data.

Arm/Group Title	Ketamine
Arm/Group Description:	All subjects will receive ketamine Ketamine: All subjects will receive ketamine to induce glutamate release in the brain
Overall Number of Participants Analyzed	27
Mean (Standard Deviation); Unit of Measure: percentage reduction
HC % reduction from baseline immediately post ket	19 (22)
MDD % reduction from baseline immediately post ket	14 (9)
HC % reduction from baseline 24 hrs post ket	31 (30)
MDD % reduction from baseline 24 hrs post ket	14 (13)

Adverse Events

Time Frame	4 years
Adverse Event Reporting Description	Standard assessments and regular observations are used to determine whether or not certain adverse events have occurred.
Arm/Group Title	Ketamine
Arm/Group Description	All subjects will receive ketamine Ketamine: All subjects will receive ketamine to induce glutamate release in the brain
All-Cause Mortality
	Ketamine
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Ketamine
	Affected / at Risk (%)	# Events
Total	1/38 (2.63%)
General disorders
post-ketamine non-responsiveness † [1]	1/38 (2.63%)	1
† Indicates events were collected by systematic assessment; [1] Post-ketamine subject was non-responsive to questions- did not respond to verbal arousal. Subject was clinically stable. Sent to ER where it was believed the experience was dissociative event due to ketamine.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Ketamine
	Affected / at Risk (%)	# Events
Total	0/38 (0.00%)

Limitations and Caveats

Study lacks placebo control group Hemodynamic effects of ketamine may alter tracer delivery and washout Study lacks long-term follow up Only non-smokers studied Ketamine dose administered is higher than typical dose used for clinical purposes

More Information

Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

• Name/Title: Irina Esterlis, Ph.D.
• Organization: Yale University - Psychiatry Department
• Phone: (203)737-6820
• EMail: irina.esterlis@yale.edu

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01691092
• Other Study ID Numbers: 1111009365
• First Submitted: September 19, 2012
• First Posted: September 24, 2012
• Results First Submitted: December 21, 2016
• Results First Posted: April 21, 2017
• Last Update Posted: April 21, 2017