Trial Outcomes & Findings for The BIomarker Guided (BIG) Study for Depression (NCT NCT04181736)

NCT ID: NCT04181736

Last Updated: 2025-03-20

Results Overview

During functional magnetic resonance imaging (fMRI), the cognitive control circuit was engaged by a Go-NoGo task, and circuit activation was quantified by blood flow in three regions of interest in the brain (dorsal anterior cingulate cortex \[dACC\], left dorsolateral prefrontal cortex \[dLPFC\], and right dLPFC) and the extent of functional connectivity between them. Task-evoked activation and connectivity are expressed as Z-scores, which represent the number of standard deviations the observed value is from the mean of a healthy reference dataset (population mean = 0). There is no fixed minimum or maximum for Z-scores. Standard deviations above the mean (a positive Z-score) indicate that the observed activation or connectivity is higher than the mean of the healthy reference dataset, while standard deviations below the mean (a negative Z-score) indicate it is lower. A negative Z-score indicates a worse outcome. For this study, a Z-score of \<= -0.5 indicates poor cognitive control.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 28 participants
• Primary outcome timeframe: pre-treatment, 8 weeks
• Results posted on: 2025-03-20

Participant Flow

Participant milestones

Measure	Guanfacine Treatment Group Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Overall Study STARTED	28
Overall Study Met Mechanistic Imaging Criteria	24
Overall Study Completed at Least 6 Weeks of Guanfacine	17
Overall Study COMPLETED	17
Overall Study NOT COMPLETED	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The BIomarker Guided (BIG) Study for Depression

Baseline characteristics by cohort

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Age, Continuous	31.4 years STANDARD_DEVIATION 11.1 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Race/Ethnicity, Customized Asian	7 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	5 Participants n=5 Participants
Race/Ethnicity, Customized More than 2 races	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants
Region of Enrollment United States	17 Participants n=5 Participants
Cognitive Control Circuit Function Z-score Dorsal anterior cingulate cortex (dACC) activation	-0.688 Z-score STANDARD_DEVIATION 0.580 • n=5 Participants
Cognitive Control Circuit Function Z-score Left dorsolateral prefrontal cortex (dLPFC) activation	-0.892 Z-score STANDARD_DEVIATION 1.205 • n=5 Participants
Cognitive Control Circuit Function Z-score Right dLPFC activation	-0.796 Z-score STANDARD_DEVIATION 0.233 • n=5 Participants
Cognitive Control Circuit Function Z-score Left dLPFC - dACC connectivity	-0.017 Z-score STANDARD_DEVIATION 0.394 • n=5 Participants
Cognitive Control Circuit Function Z-score Right dLPFC - dACC connectivity	0.161 Z-score STANDARD_DEVIATION 0.564 • n=5 Participants
17-item Hamilton Depression Rating Scale (HDRS-17)	16.765 score on a scale STANDARD_DEVIATION 3.437 • n=5 Participants
Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR)	13.941 score on a scale STANDARD_DEVIATION 3.848 • n=5 Participants
Cognitive Control Behavioral Performance Z-score Maze	0.230 Z-score STANDARD_DEVIATION 0.568 • n=5 Participants
Cognitive Control Behavioral Performance Z-score Digit Span	-0.066 Z-score STANDARD_DEVIATION 1.507 • n=5 Participants
Cognitive Control Behavioral Performance Z-score Verbal Interference (Stroop) Word	-0.674 Z-score STANDARD_DEVIATION 0.708 • n=5 Participants
Cognitive Control Behavioral Performance Z-score Verbal Interference (Stroop) Color	0.134 Z-score STANDARD_DEVIATION 1.168 • n=5 Participants
Cognitive Control Behavioral Performance Z-score Switching of Attention (Trails B)	0.301 Z-score STANDARD_DEVIATION 0.789 • n=5 Participants
Cognitive Control Behavioral Performance Z-score GoNoGo Reaction Time	0 Z-score STANDARD_DEVIATION 1 • n=5 Participants
World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Score Physical Health	52.647 transformed score on a scale STANDARD_DEVIATION 13.124 • n=5 Participants
World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Score Psychological Health	31.294 transformed score on a scale STANDARD_DEVIATION 12.712 • n=5 Participants
World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Score Social Relationships	40.059 transformed score on a scale STANDARD_DEVIATION 16.566 • n=5 Participants
World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Score Environment	59.706 transformed score on a scale STANDARD_DEVIATION 14.632 • n=5 Participants
Satisfaction With Life Scale (SWLS) Score	13.471 score on a scale STANDARD_DEVIATION 4.017 • n=5 Participants
Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score	0.706 score on a scale STANDARD_DEVIATION 1.047 • n=5 Participants

PRIMARY outcome

Timeframe: pre-treatment, 8 weeks

Population: Participants who completed at least 6 weeks of guanfacine.

During functional magnetic resonance imaging (fMRI), the cognitive control circuit was engaged by a Go-NoGo task, and circuit activation was quantified by blood flow in three regions of interest in the brain (dorsal anterior cingulate cortex [dACC], left dorsolateral prefrontal cortex [dLPFC], and right dLPFC) and the extent of functional connectivity between them. Task-evoked activation and connectivity are expressed as Z-scores, which represent the number of standard deviations the observed value is from the mean of a healthy reference dataset (population mean = 0). There is no fixed minimum or maximum for Z-scores. Standard deviations above the mean (a positive Z-score) indicate that the observed activation or connectivity is higher than the mean of the healthy reference dataset, while standard deviations below the mean (a negative Z-score) indicate it is lower. A negative Z-score indicates a worse outcome. For this study, a Z-score of <= -0.5 indicates poor cognitive control.

Outcome measures

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Change in Cognitive Control Circuit Function Z-score Change in dorsal anterior cingulate cortex (dACC) activation	0.350 Z-score Standard Deviation 0.617
Change in Cognitive Control Circuit Function Z-score Change in right dLPFC Activation	0.105 Z-score Standard Deviation 0.361
Change in Cognitive Control Circuit Function Z-score Change in R dLPFC - dACC Connectivity	-0.153 Z-score Standard Deviation 0.713
Change in Cognitive Control Circuit Function Z-score Change in left dLPFC activation	0.441 Z-score Standard Deviation 1.058
Change in Cognitive Control Circuit Function Z-score Change in L dLPFC - dACC Connectivity	0.324 Z-score Standard Deviation 0.485

SECONDARY outcome

Timeframe: 8 weeks

Population: Participants who completed at least 6 weeks of guanfacine.

Possible HDRS-17 scores range from 0 (no depression) to 52 (severe depression).

Outcome measures

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Number of Participants With a Score of ≤7 on the 17-item Hamilton Depression Rating Scale (HDRS-17) at Week 8 as a Measure of Depression Remission.	11 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Participants who completed at least 6 weeks of guanfacine.

Possible QIDS-SR scores range from 0 (no depression) to 27 (severe depression).

Outcome measures

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Number of Participants With a Score ≤5 on the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) at Week 8 as a Measure of Depression Remission.	6 Participants

SECONDARY outcome

Timeframe: pre-treatment, 8 weeks

Population: Participants who completed at least 6 weeks of guanfacine.

Possible HDRS-17 scores range from 0 (no depression) to 52 (severe depression).

Outcome measures

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Number of Participants With a ≥50% Reduction on the 17-item Hamilton Depression Rating Scale (HDRS-17) as a Measure of Depression Response.	13 Participants

SECONDARY outcome

Timeframe: pre-treatment, 8 weeks

Population: Participants who completed at least 6 weeks of guanfacine.

Possible QIDS-SR scores range from 0 (no depression) to 27 (severe depression).

Outcome measures

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Number of Participants With a ≥50% Reduction From Baseline on the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) as a Measure of Depression Response.	7 Participants

SECONDARY outcome

Timeframe: baseline, 2 weeks, 8 weeks

Population: Participants who completed at least 6 weeks of guanfacine.

Possible HDRS-17 scores range from 0 (no depression) to 52 (severe depression).

Outcome measures

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Change in Depression Scores on the 17-item Hamilton Depression Rating Scale (HDRS-17) Change from baseline to 2 weeks	5.875 units on a scale Standard Deviation 3.998
Change in Depression Scores on the 17-item Hamilton Depression Rating Scale (HDRS-17) Change from baseline to 8 weeks	9.529 units on a scale Standard Deviation 3.023

SECONDARY outcome

Timeframe: pre-treatment, 2 weeks, 4 weeks, 6 weeks, 8 weeks

Population: Participants who received at least 6 weeks of guanfacine.

Possible QIDS-SR scores range from 0 (no depression) to 27 (severe depression).

Outcome measures

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Change in Depression Scores on the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) Change in QIDS-SR scores from baseline to 2 weeks	3.000 score on a scale Standard Deviation 2.633
Change in Depression Scores on the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) Change in QIDS-SR scores from baseline to 4 weeks	-4.929 score on a scale Standard Deviation 2.556
Change in Depression Scores on the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) Change in QIDS-SR scores from baseline to 6 weeks	-5.200 score on a scale Standard Deviation 2.394
Change in Depression Scores on the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) Change in QIDS-SR scores from baseline to 8 weeks	-5.353 score on a scale Standard Deviation 4.286

SECONDARY outcome

Timeframe: pre-treatment, 8 weeks

Population: Participants who completed at least 6 weeks of guanfacine.

Cognitive control behavioral performance was assessed using the WebNeuro computerized battery measuring cognitive control. Test performance is expressed as a composite Z-score, representing deviations from the mean of a healthy reference dataset (population mean = 0). Composite Z-scores were calculated by averaging: Maze (trials completed, completion and path learning time, errors), Digit Span (recall span, correct trials), Verbal Interference (total errors, reaction time), and Switching of Attention (completion time, connection time, errors). For GoNoGo, only reaction times were used as data was collected in-scanner, and data for this measure was normalized to the group. Extreme scores were winsorized to a threshold of 5 standard deviations. Z-scores have no fixed range; positive scores indicate better performance, negative scores indicate worse performance. For this study, a Z-score of <= -0.5 indicates poor cognitive control performance.

Outcome measures

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Change in Cognitive Control Behavioral Performance Z-score Verbal Interference (Stroop) Color	0.082 Z-score Standard Deviation 0.776
Change in Cognitive Control Behavioral Performance Z-score Change in Switching of Attention (Trails B)	0.341 Z-score Standard Deviation 0.798
Change in Cognitive Control Behavioral Performance Z-score Change in GoNoGo Reaction Time	1.584 Z-score Standard Deviation 2.048
Change in Cognitive Control Behavioral Performance Z-score Change in Maze	-0.076 Z-score Standard Deviation 0.859
Change in Cognitive Control Behavioral Performance Z-score Change in Digit Span	0.332 Z-score Standard Deviation 1.349
Change in Cognitive Control Behavioral Performance Z-score Change in Verbal Interference (Stroop) Word	0.273 Z-score Standard Deviation 0.336

SECONDARY outcome

Timeframe: pre-treatment, 2 weeks, 8 weeks

Population: Participants who completed at least 6 weeks of guanfacine.

Possible scores on the SWLS range from 5 (extreme dissatisfaction) to 35 (extreme satisfaction).

Outcome measures

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Change in the Satisfaction With Life Scale (SWLS) Score Change from baseline to 2 weeks	-1.104 units on a scale Standard Deviation 2.901
Change in the Satisfaction With Life Scale (SWLS) Score Change from baseline to 8 weeks	5.529 units on a scale Standard Deviation 2.746

SECONDARY outcome

Timeframe: pre-treatment, 2 weeks, 8 weeks

Population: Participants who completed at least 6 weeks of guanfacine.

Scores on the WHOQOL-BREF are transformed to a scale of 0 (poor quality of life) to 100 (excellent quality of life).

Outcome measures

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Change in the World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Scale Score Change in Psychological Health from baseline to 8 weeks	-15.118 units on a transformed scale Standard Deviation 3.909
Change in the World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Scale Score Change in Social Relationships from baseline to 8 weeks	-7.353 units on a transformed scale Standard Deviation 3.056
Change in the World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Scale Score Change in Environment from baseline to 8 weeks	-1.875 units on a transformed scale Standard Deviation 2.802
Change in the World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Scale Score Change in Physical Health from baseline to 2 weeks	-2.438 units on a transformed scale Standard Deviation 1.276
Change in the World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Scale Score Change in Psychological Health from baseline to 2 weeks	-6.562 units on a transformed scale Standard Deviation 2.158
Change in the World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Scale Score Change in Social Relationships from baseline to 2 weeks	-5.125 units on a transformed scale Standard Deviation 1.882
Change in the World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Scale Score Change in Environment from baseline to 2 weeks	-1.875 units on a transformed scale Standard Deviation 2.802
Change in the World Health Organization Quality of Life - Brief (WHOQOL-BREF) Scale Scale Score Change in Physical Health from baseline to 8 weeks	-9.235 units on a transformed scale Standard Deviation 1.315

SECONDARY outcome

Timeframe: pre-treatment, 8 weeks

Possible scores on the C-SSRS ideation range from 0 (no suicidal ideation) to 5 (high suicidal ideation).

Outcome measures

Measure	Guanfacine Treatment Group n=17 Participants Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Change in the Columbia-Suicide Severity Rating Scale (C-SSRS) Ideation Score	-0.176 score on a scale Standard Deviation 0.883

Adverse Events

Guanfacine Treatment Group

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	Guanfacine Treatment Group n=28 participants at risk Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Psychiatric disorders Increased Suicidality	3.6% 1/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)

Other adverse events

Measure	Guanfacine Treatment Group n=28 participants at risk Participants are prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study clinicians. Participants start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.
Gastrointestinal disorders Dry Mouth	64.3% 18/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Nervous system disorders Daytime Fatigue	42.9% 12/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Nervous system disorders Dizziness	28.6% 8/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Psychiatric disorders Difficulty Sleeping	25.0% 7/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Nervous system disorders Headache	21.4% 6/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Nervous system disorders Paresthesias	14.3% 4/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Gastrointestinal disorders Constipation	14.3% 4/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Cardiac disorders Heart Palpitations	10.7% 3/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Gastrointestinal disorders Reduced Appetite	10.7% 3/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Nervous system disorders Transient Tinnitus	3.6% 1/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Respiratory, thoracic and mediastinal disorders Shortness of Breath	3.6% 1/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Psychiatric disorders Irritability	3.6% 1/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)
Gastrointestinal disorders Acid reflux	3.6% 1/28 • 10 weeks (8 weeks treatment plus 2 week follow-up)

Additional Information

Laura Hack, MD, PhD

Stanford University

Phone: 650-724-7478

Email: lhack@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place