Trial Outcomes & Findings for Pharmacologic Augmentation of Targeted Cognitive Training in Schizophrenia (NCT NCT04414930)

NCT ID: NCT04414930

Last Updated: 2025-12-17

Results Overview

Positive \& Negative Symptom Scale total (PANSSt) PANSS Total Score is the primary clinical outcome measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks). The PANSS total score has a range 30-210, with higher scores indicating worse outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 68 participants
• Primary outcome timeframe: approximately 10 weeks
• Results posted on: 2025-12-17

Participant Flow

Antipsychotic-medicated outpatients with a primary diagnosis of SZ or schizoaffective disorder (depressed type) ages 18-55 were recruited from the San Diego community between 11/9/2020 and 3/13/2024. Of the 68 consented/enrolled participants, 28 met inclusion criteria and were randomized to treatment.

A total of 68 participants were enrolled but 35 were excluded for not meeting inclusion criteria and 5 withdrew from the study. Therefore 28 participants were randomized.

Participant milestones

Measure	Placebo Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Amphetamine Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.
Overall Study STARTED	10	18
Overall Study COMPLETED	9	15
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Measure	Placebo Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Amphetamine Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.
Overall Study Withdrawal by Subject	1	3

Baseline Characteristics

Pharmacologic Augmentation of Targeted Cognitive Training in Schizophrenia

Baseline characteristics by cohort

Measure	Placebo n=10 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Active Drug n=18 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.	Total n=28 Participants Total of all reporting groups
Age, Continuous	41.7 years n=6 Participants	46.7 years n=5 Participants	44.9 years n=5 Participants
Sex: Female, Male Female	5 Participants n=6 Participants	8 Participants n=5 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=6 Participants	10 Participants n=5 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=6 Participants	5 Participants n=5 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=6 Participants	13 Participants n=5 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=6 Participants	0 Participants n=5 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=6 Participants	2 Participants n=5 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=6 Participants	0 Participants n=5 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=6 Participants	5 Participants n=5 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=6 Participants	9 Participants n=5 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=6 Participants	2 Participants n=5 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=6 Participants	0 Participants n=5 Participants	1 Participants n=5 Participants
Region of Enrollment United States	10 participants n=6 Participants	18 participants n=5 Participants	28 participants n=5 Participants

PRIMARY outcome

Timeframe: approximately 10 weeks

Positive & Negative Symptom Scale total (PANSSt) PANSS Total Score is the primary clinical outcome measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks).

The PANSS total score has a range 30-210, with higher scores indicating worse outcome.

Outcome measures

Measure	Placebo n=10 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Amphetamine n=18 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.
Primary Clinical Outcome PANSS Total Score (PANSSt) Baseline	65.4 score on a scale Standard Error 5.7	55.6 score on a scale Standard Error 3.2
Primary Clinical Outcome PANSS Total Score (PANSSt) Post-10	67.1 score on a scale Standard Error 4.6	49.8 score on a scale Standard Error 3.1
Primary Clinical Outcome PANSS Total Score (PANSSt) Post-20	61.0 score on a scale Standard Error 5.7	50.5 score on a scale Standard Error 2.5
Primary Clinical Outcome PANSS Total Score (PANSSt) Post-30	60.1 score on a scale Standard Error 7.3	46.5 score on a scale Standard Error 2.2

PRIMARY outcome

Timeframe: approximately 10 weeks

Primary World Health Organization Disability Schedule (WHODAS 2.0) Function will be assessed via the World Health Organization Disability Schedule 2.0 (WHODAS 2.0) at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks). The WHODAS 2.0 has a range 12-60, with higher scores indicating worse outcome.

Outcome measures

Measure	Placebo n=10 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Amphetamine n=18 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.
Primary Functional Outcome WHODAS Baseline	26.6 score on a scale Standard Error 4.7	53.1 score on a scale Standard Error 8.0
Primary Functional Outcome WHODAS Post-10	38.1 score on a scale Standard Error 9.4	43.7 score on a scale Standard Error 7.2
Primary Functional Outcome WHODAS Post-20	29.6 score on a scale Standard Error 6.8	34.5 score on a scale Standard Error 8.7
Primary Functional Outcome WHODAS Post-30	34.7 score on a scale Standard Error 8.9	32.1 score on a scale Standard Error 4.8

PRIMARY outcome

Timeframe: approximately 10 weeks

MATRICS Consensus Cognitive Battery Global Composite T-score (MCCB-C) The MCCB Global Composite T-score (MCCB-C) is the primary neurocognitive outcome measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks). The MATRICS Consensus Cognitive Battery (MCCB) composite T-score has no minimum or maximum score because it uses T-scores, which are standardized based on a community sample. A normal range MCCB composite T-score is between 40 and 60 and higher scores indicate better neurocognitive outcome.

Outcome measures

Measure	Placebo n=10 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Amphetamine n=18 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.
Primary Neurocognitive Outcome MCCB-C Baseline	17.7 score on a scale Standard Error 3.2	29.8 score on a scale Standard Error 5.0
Primary Neurocognitive Outcome MCCB-C Post-10	19.3 score on a scale Standard Error 4.9	30.4 score on a scale Standard Error 5.1
Primary Neurocognitive Outcome MCCB-C Post-20	21.3 score on a scale Standard Error 3.8	34.3 score on a scale Standard Error 4.6
Primary Neurocognitive Outcome MCCB-C Post-30	20.3 score on a scale Standard Error 4.7	30.5 score on a scale Standard Error 4.8

SECONDARY outcome

Timeframe: approximately 10 weeks

Positive & Negative Symptom Scale positive symptom subscale (PANSSp) measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks). The PANSSp is rated with 1 to 7 points ranging from absent to extreme. The range is 7-49 and higher scores indicate worse outcome.

Outcome measures

Measure	Placebo n=10 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Amphetamine n=18 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.
Secondary Clinical Outcome Measure PANSSp Post-30	14.7 score on a scale Standard Error 1.9	11.8 score on a scale Standard Error 0.8
Secondary Clinical Outcome Measure PANSSp Post-20	16.0 score on a scale Standard Error 1.9	13.9 score on a scale Standard Error 1.1
Secondary Clinical Outcome Measure PANSSp Baseline	16.6 score on a scale Standard Error 2.3	15.2 score on a scale Standard Error 1.3
Secondary Clinical Outcome Measure PANSSp Post-10	16.6 score on a scale Standard Error 2.0	12.5 score on a scale Standard Error 1.0

SECONDARY outcome

Timeframe: approximately 10 weeks

Positive & Negative Symptom Scale negative symptom subscale (PANSSn)measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks). The PANSSn is rated with 1 to 7 points ranging from absent to extreme. The range is 7-49 and higher scores indicate worse outcome.

Outcome measures

Measure	Placebo n=10 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Amphetamine n=18 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.
Secondary Clinical Outcome Measure PANSSn Baseline	16.6 score on a scale Standard Error 2.1	12.8 score on a scale Standard Error 1.1
Secondary Clinical Outcome Measure PANSSn Post-10	17.4 score on a scale Standard Error 1.4	12.9 score on a scale Standard Error 1.3
Secondary Clinical Outcome Measure PANSSn Post-20	15.9 score on a scale Standard Error 2.6	12.1 score on a scale Standard Error 0.7
Secondary Clinical Outcome Measure PANSSn Post-30	17.4 score on a scale Standard Error 3.1	12.0 score on a scale Standard Error 0.8

SECONDARY outcome

Timeframe: approximately 10 weeks

Psychotic Symptom Rating Scales (PSYRATS hallucination subscale) assesses auditory hallucinations measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks). The PSYRATS auditory hallucinations subscale (AHS) consisting of 11 items, with each item being rated from 0 (absent) to 4 (severe), range 0-44, with higher scores indicating more severe auditory hallucinations or worse outcome.

Outcome measures

Measure	Placebo n=10 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Amphetamine n=18 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.
Psychotic Symptoms PSYRATS Hallucinations Post-20	5.6 score on a scale Standard Error 2.9	13.9 score on a scale Standard Error 2.7
Psychotic Symptoms PSYRATS Hallucinations Post-30	0.0 score on a scale Standard Error 0.0	10.4 score on a scale Standard Error 3.1
Psychotic Symptoms PSYRATS Hallucinations Baseline	2.7 score on a scale Standard Error 1.8	16.3 score on a scale Standard Error 2.8
Psychotic Symptoms PSYRATS Hallucinations Post-10	3.4 score on a scale Standard Error 3.4	11.3 score on a scale Standard Error 2.9

SECONDARY outcome

Timeframe: approximately 10 weeks

Young Mania Rating Scale total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks). The range for the YMRS total score is 0-60, with higher scores indicating more severe manic symptoms or worse outcome.

Outcome measures

Measure	Placebo n=10 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Amphetamine n=18 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.
Manic Symptoms YMRS Post-10	6.0 score on a scale Standard Error 1.4	2.6 score on a scale Standard Error 1.0
Manic Symptoms YMRS Post-30	6.0 score on a scale Standard Error 1.9	2.5 score on a scale Standard Error 0.7
Manic Symptoms YMRS Post-20	5.9 score on a scale Standard Error 2.1	3.3 score on a scale Standard Error 1.0
Manic Symptoms YMRS Baseline	7.0 score on a scale Standard Error 2.1	5.6 score on a scale Standard Error 1.4

SECONDARY outcome

Timeframe: approximately 10 weeks

Patient Health Questionnaire-9 (PHQ-9) total score measured at baseline vs. post-TCT session 10, 20 and 30 (approximately 10 weeks). The PHQ-9 has a range from 0 to 27 with higher scores indicating more severe depression or worse outcome.

Outcome measures

Measure	Placebo n=10 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Amphetamine n=18 Participants Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.
Current Depressive Symptoms PHQ Baseline	4.4 score on a scale Standard Error 1.4	6.3 score on a scale Standard Error 1.7
Current Depressive Symptoms PHQ Post-10	6.3 score on a scale Standard Error 1.7	2.9 score on a scale Standard Error 0.9
Current Depressive Symptoms PHQ Post-20	4.0 score on a scale Standard Error 1.3	4.4 score on a scale Standard Error 1.9
Current Depressive Symptoms PHQ Post-30	3.9 score on a scale Standard Error 2.1	3.9 score on a scale Standard Error 1.2

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Amphetamine

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=10 participants at risk Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Placebo: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.	Amphetamine n=18 participants at risk Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. d-amphetamine: Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training.
Psychiatric disorders increase in psychiatric symptoms	30.0% 3/10 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".	22.2% 4/18 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".
Gastrointestinal disorders Gastrointestinal	20.0% 2/10 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".	16.7% 3/18 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".
Psychiatric disorders Restless night	10.0% 1/10 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".	16.7% 3/18 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".
Nervous system disorders Worsening TD-related tremor	10.0% 1/10 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".	0.00% 0/18 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".
General disorders Minor Accident (e.g. trip, fall)	10.0% 1/10 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".	5.6% 1/18 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".
Cardiac disorders Elevated blood pressure and/or heart rate	10.0% 1/10 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".	11.1% 2/18 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".
Ear and labyrinth disorders ear ache	10.0% 1/10 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".	0.00% 0/18 • Data was collected over the course of the study participation, about 10 weeks Gastrointestinal symptoms (e.g. bloating, diarrhea, cramps) were all assessed/monitored under the general description "gastrointestinal symptoms".

Additional Information

Neal R. Swerdlow, M.D., Ph.D.

UCSD

Phone: 6194719455

Email: nswerdlow@health.ucsd.edu

Results disclosure agreements

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