Trial Outcomes & Findings for Advancing Personalized Antidepressant Treatment Using PET/MRI (NCT NCT02623205)

Last Updated: 2022-12-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

85 participants

Primary outcome timeframe

8 weeks

Results posted on

2022-12-15

Participant Flow

Participant milestones

Participant milestones
Measure	Escitalopram 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.	Placebo 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.
Overall Study STARTED	42	43
Overall Study COMPLETED	38	40
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Escitalopram 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.	Placebo 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.
Overall Study Lost to Follow-Up or Discontinued Intervention	4	3

Baseline Characteristics

Advancing Personalized Antidepressant Treatment Using PET/MRI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Escitalopram n=42 Participants 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.	Placebo n=43 Participants 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 n=85 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	42 Participants n=5 Participants	43 Participants n=7 Participants	85 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	29 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity Categories · Caucasian - White	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity Categories · Caucasian - Non-white	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity Categories · African American / Black	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity Categories · Asian - South Asian	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity Categories · Asian - East Asian	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity Categories · Asian - Southeast Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity Categories · Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity Categories · Mixed	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment United States	42 participants n=5 Participants	43 participants n=7 Participants	85 participants n=5 Participants
Hamilton Depression Scale (HAM-D) Rating	18.86 Scores on Scale STANDARD_DEVIATION 5.09 • n=5 Participants	16.79 Scores on Scale STANDARD_DEVIATION 3.84 • n=7 Participants	17.81 Scores on Scale STANDARD_DEVIATION 4.59 • n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: 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)

Outcome measures

Outcome measures
Measure	Escitalopram n=31 Participants 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.	Placebo n=32 Participants 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.
Change From Baseline in Hamilton Depression Rating Scale at 8 Weeks	11.81 score on a scale Standard Deviation 7.02	9.41 score on a scale Standard Deviation 5.66

SECONDARY outcome

Timeframe: 8 weeks

Population: 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.

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/

Outcome measures

Outcome measures
Measure	Escitalopram n=29 Participants 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.	Placebo n=29 Participants 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.
Change From Baseline in Metabolic Rate of Glucose (MRGlu), Quantified Using Arterial Blood Analysis, at 8 Weeks	0.507489448 mg/(min*100 ml) Standard Deviation 0.102327217	0.068629964 mg/(min*100 ml) Standard Deviation 0.048866182

SECONDARY outcome

Timeframe: Baseline

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Escitalopram n=48 Participants 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.	Placebo 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.
Quantification of Brain MRGlu Without an Arterial Catheter by Training Simultaneous Estimation (SimE)	2.0 Percent of Activity Standard Deviation 7.1	—

SECONDARY outcome

Timeframe: Baseline

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Escitalopram n=5 Participants 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.	Placebo 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.
Bias of VersaPET Scanner From Measurements Taken at the Wrist and Ankle	5 Percent	—

SECONDARY outcome

Timeframe: Baseline

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.

Outcome measures

Outcome measures
Measure	Escitalopram n=5 Participants 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.	Placebo 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.
Correlation Coefficient of VersaPET Scanner From Measurements Taken at the Wrist or Ankle	0.97 Correlation Coefficient	—

Adverse Events

Escitalopram

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Kathryn Hill

Department of Psychiatry, Renaissance School of Medicine at Stony Brook University

Phone: 904-252-3449

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place