Advancing Personalized Antidepressant Treatment Using PET/MRI

• ClinicalTrials.gov Identifier: NCT02623205
• Recruitment Status: Completed
• First Posted: December 7, 2015
• Results First Posted: June 2, 2022
• Last Update Posted: December 15, 2022
• Sponsor: Stony Brook University
• Information provided by (Responsible Party): Christine DeLorenzo, Stony Brook University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Depression
• Interventions: Drug: Escitalopram; Drug: Placebo
• Enrollment: 85

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Escitalopram	Placebo
Arm/Group Description	Active Comparator: Escitalopram (Lexapro) 10mg Week 1, 20mg Weeks 2 and 3, and 30mg for Weeks 4 to 8 (or until 12 for patients close to remission) Escitalopram: Participants randomized to the escitalopram group will be given the medication for 8 weeks, after which they will be given the option to continue for 4 more weeks if they are close to remission.	Lactose pill manufactured to mimic Escitalopram pill Placebo: To reduce the burden of the patients on placebo, the placebo trial will have a target of 8 weeks. To provide an opportunity for placebo non-responders to receive active drug and to aid in recruitment, we will provide 8-12 weeks of selective serotonin reuptake inhibitor (SSRI) treatment to placebo non-responders.
Period Title: Overall Study
Started	42	43
Completed	38	40
Not Completed	4	3
Reason Not Completed
Lost to Follow-Up or Discontinued Intervention	4	3

Baseline Characteristics

Arm/Group Title		Escitalopram	Placebo	Total
Arm/Group Description		Active Comparator: Escitalopram (Lexapro) 10mg Week 1, 20mg Weeks 2 and 3, and 30mg for Weeks 4 to 8 (or until 12 for patients close to remission) Escitalopram: Participants randomized to the escitalopram group will be given the medication for 8 weeks, after which they will be given the option to continue for 4 more weeks if they are close to remission.	Lactose pill manufactured to mimic Escitalopram pill Placebo: To reduce the burden of the patients on placebo, the placebo trial will have a target of 8 weeks. To provide an opportunity for placebo non-responders to receive active drug and to aid in recruitment, we will provide 8-12 weeks of SSRI treatment to placebo non-responders.	Total of all reporting groups
Overall Number of Baseline Participants		42	43	85
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants	43 participants	85 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	42 100.0%	43 100.0%	85 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	42 participants	43 participants	85 participants
	Female	27 64.3%	29 67.4%	56 65.9%
	Male	15 35.7%	14 32.6%	29 34.1%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race/Ethnicity Categories	Number Analyzed	42 participants	43 participants	85 participants
	Caucasian - White	26 61.9%	26 60.5%	52 61.2%
	Caucasian - Non-white	2 4.8%	1 2.3%	3 3.5%
	African American / Black	2 4.8%	2 4.7%	4 4.7%
	Asian - South Asian	5 11.9%	2 4.7%	7 8.2%
	Asian - East Asian	3 7.1%	4 9.3%	7 8.2%
	Asian - Southeast Asian	0 0.0%	1 2.3%	1 1.2%
	Pacific Islander	0 0.0%	1 2.3%	1 1.2%
	Mixed	4 9.5%	6 14.0%	10 11.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	42 participants	43 participants	85 participants
		42	43	85
Hamilton Depression Scale (HAM-D) Rating [1]; Mean (Standard Deviation); Unit of measure: Scores on Scale
	Number Analyzed	42 participants	43 participants	85 participants
		18.86 (5.09)	16.79 (3.84)	17.81 (4.59)
		[1] Measure Description: Hamilton Depression Scale. Scale is from 0 to 52. The higher the score on the scale, the more severe the degree of depression.

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hamilton Depression Rating Scale at 8 Weeks
Description	Comparison of Hamilton Depression Rating Scale-17 score at pretreatment and post-treatment. Minimum score 0, maximum possible score 52, with remission defined as <=7. The higher the score on the scale, the more severe the degree of depression.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Disparity in Week 8 Number Analyzed versus Baseline Number Enrolled due to participants lost to follow up or instances of discontinued intervention (Escitalopram Group: n = 4, Placebo Group: n =3), and participants who were excluded from analysis for one of the following: Greater than 20% blood glucose change between pre-scan and post scan sampling, Diabetes, Motion Interference, & Instrument Failure (Escitalopram Group: n = 7, Placebo Group: n = 8)

Arm/Group Title	Escitalopram	Placebo
Arm/Group Description:	Active Comparator: Escitalopram (Lexapro) 10mg Week 1, 20mg Weeks 2 and 3, and 30mg for Weeks 4 to 8 (or until 12 for patients close to remission) Escitalopram: Participants randomized to the escitalopram group will be given the medication for 8 weeks, after which they will be given the option to continue for 4 more weeks if they are close to remission.	Lactose pill manufactured to mimic Escitalopram pill Placebo: To reduce the burden of the patients on placebo, the placebo trial will have a target of 8 weeks. To provide an opportunity for placebo non-responders to receive active drug and to aid in recruitment, we will provide 8-12 weeks of SSRI treatment to placebo non-responders.
Overall Number of Participants Analyzed	31	32
Mean (Standard Deviation); Unit of Measure: score on a scale
	11.81 (7.02)	9.41 (5.66)

2. Secondary Outcome

Title	Change From Baseline in Metabolic Rate of Glucose (MRGlu), Quantified Using Arterial Blood Analysis, at 8 Weeks
Description	Difference between MRGlu Metabolism in Right Insular Cortex before treatment (baseline) and after treatment (week 8). Details on methods and criteria used to assess brain glucose metabolism rates can be found here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551925/
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Total n = 15 excluded from analysis for the following: Greater than 20% blood glucose change between pre-scan and post scan sampling, Motion, Instrument failure. In addition, several participants in each group were lost to follow up or discontinued intervention.

Arm/Group Title	Escitalopram	Placebo
Arm/Group Description:	Active Comparator: Escitalopram (Lexapro) 10mg Week 1, 20mg Weeks 2 and 3, and 30mg for Weeks 4 to 8 (or until 12 for patients close to remission) Escitalopram: Participants randomized to the escitalopram group will be given the medication for 8 weeks, after which they will be given the option to continue for 4 more weeks if they are close to remission.	Lactose pill manufactured to mimic Escitalopram pill Placebo: To reduce the burden of the patients on placebo, the placebo trial will have a target of 8 weeks. To provide an opportunity for placebo non-responders to receive active drug and to aid in recruitment, we will provide 8-12 weeks of SSRI treatment to placebo non-responders.
Overall Number of Participants Analyzed	29	29
Mean (Standard Deviation); Unit of Measure: mg/(min*100 ml)
	0.507489448 (0.102327217)	0.068629964 (0.048866182)

3. Secondary Outcome

Title	Quantification of Brain MRGlu Without an Arterial Catheter by Training Simultaneous Estimation (SimE)
Description	Using Simultaneous Estimation, we imputed the arterial input function from a single venous sample. When we compared the resulting imputed arterial input function to the actual arterial input function collected from plasma samples, we calculated the percent difference in activity and report it here.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

This measure occurred before treatment had been started, and was independent of treatment condition, therefore participants were not stratified by Arm. Once this method had been validated, we did not continue to acquire samples with arterial lines, hence why only a subset of the participants were analyzed.

Arm/Group Title	Mixed
Arm/Group Description:	This group consisted of both Escitalopram & Placebo treated subjects. Participants were not stratified by arm, as that is unrelated to Outcome Measure.
Overall Number of Participants Analyzed	48
Mean (Standard Deviation); Unit of Measure: Percent of Activity
	2.0 (7.1)

4. Secondary Outcome

Title	Bias of VersaPET Scanner From Measurements Taken at the Wrist and Ankle
Description	Our goal was to determine the Bias of plasma radioactivity measurements taken at the ankle with a Novel Positron Emission Tomography (VersaPET) Scanner compared to radioactivity from arterial sampling taken at the wrist. Bias refers to the offset between the ground truth and estimated data. A bias of 0% is ideal.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

This measure occurred before treatment had been started, and was independent of treatment condition, therefore all subjects analyzed were grouped into one mixed arm of both drug and placebo-assigned participants. This analysis required specialized equipment that wasn't always available, so only a subset of subjects participated.

Arm/Group Title	Mixed
Arm/Group Description:	This group consisted of both Escitalopram & Placebo treated subjects. Participants were not stratified by arm, as that is unrelated to Outcome Measure.
Overall Number of Participants Analyzed	5
Measure Type: Number; Unit of Measure: Percent
	5

5. Secondary Outcome

Title	Correlation Coefficient of VersaPET Scanner From Measurements Taken at the Wrist or Ankle
Description	Arterial measurements from samples taken at the wrist were compared to the values from the VersaPET scanner (at the ankle) where the correlation coefficient between the scanner and arterial sampling are being reported. Correlation coefficient ranges from -1 to 1. The closer the value is to 1, the higher the correlation or stronger the relationship.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

This measure occurred before treatment had been started, and was independent of treatment condition, therefore all subjects analyzed were grouped into one mixed arm of both drug and placebo-assigned participants. This analysis required specialized equipment that wasn't always available, so only a subset of subjects participated.

Arm/Group Title	Mixed
Arm/Group Description:	This group consisted of both Escitalopram & Placebo treated subjects. Participants were not stratified by arm, as that is unrelated to Outcome Measure.
Overall Number of Participants Analyzed	5
Measure Type: Number; Unit of Measure: Correlation Coefficient
	0.97

Adverse Events

Time Frame	Adverse event data were collected over a period of up to 6-weeks during the pre-treatment washout phase (when necessary), and for the complete 8-week treatment period.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Escitalopram	Placebo
Arm/Group Description	Active Comparator: Escitalopram (Lexapro) 10mg Week 1, 20mg Weeks 2 and 3, and 30mg for Weeks 4 to 8 (or until 12 for patients close to remission) Escitalopram: Participants randomized to the escitalopram group will be given the medication for 8 weeks, after which they will be given the option to continue for 4 more weeks if they are close to remission.	Lactose pill manufactured to mimic Escitalopram pill Placebo: To reduce the burden of the patients on placebo, the placebo trial will have a target of 8 weeks. To provide an opportunity for placebo non-responders to receive active drug and to aid in recruitment, we will provide 8-12 weeks of SSRI treatment to placebo non-responders.
All-Cause Mortality
	Escitalopram	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/42 (0.00%)	0/43 (0.00%)
Serious Adverse Events
	Escitalopram	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/42 (0.00%)	0/43 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Escitalopram	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/42 (0.00%)	0/43 (0.00%)

Limitations and Caveats

[Not Specified]

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: Kathryn Hill
• Organization: Department of Psychiatry, Renaissance School of Medicine at Stony Brook University
• Phone: 904-252-3449
• EMail: kathryn.hill@stonybrookmedicine.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Narayan GA, Hill KR, Wengler K, He X, Wang J, Yang J, Parsey RV, DeLorenzo C. Does the change in glutamate to GABA ratio correlate with change in depression severity? A randomized, double-blind clinical trial. Mol Psychiatry. 2022 Sep;27(9):3833-3841. doi: 10.1038/s41380-022-01730-4. Epub 2022 Aug 18.

• Responsible Party: Christine DeLorenzo, Stony Brook University
• ClinicalTrials.gov Identifier: NCT02623205
• Other Study ID Numbers: 2014-2911-F
• First Submitted: December 1, 2015
• First Posted: December 7, 2015
• Results First Submitted: February 7, 2022
• Results First Posted: June 2, 2022
• Last Update Posted: December 15, 2022