SchizophreniaPhase 2NCT04414930
Pharmacologic Augmentation of Targeted Cognitive Training in Schizophrenia
A Phase 2 study testing d-amphetamine in people with Schizophrenia and Schizoaffective Disorder, run by University of California, San Diego at 1 site in United States.
Trial summary
These studies look to conduct efficient pilot testing of a novel intervention strategy for chronic psychotic disorders - Pharmacologic Augmentation of Cognitive Therapy (PACT) - via an experimental medicine approach. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- d-amphetamine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Nov 2020to 30 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- DSM-IV diagnosis of schizophrenia or schizoaffective disorder, depressed type
- Written informed consent to participate in the study
- Age 18 - 55
- Absence of dementia or mental retardation
- Urine toxicology negative for recreational drugs
- Fluent and literate in English (needed for completion of WIN and QuickSIN)
Who cannot join
- Meets DSM-IV criteria for current substance abuse or dependence and has been substance abstinent for less than 30 days
- A history of traumatic brain injury
- Auditory or visual impairments severe enough to prevent study participation
- Under conservatorship (determined by Anasazi)
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical Teaching Facility (CTF-B102) at UCSD Medical Center
San Diego, California, 92103
About this study
These studies look to conduct efficient pilot testing of a novel intervention strategy for chronic psychotic disorders - Pharmacologic Augmentation of Cognitive Therapy (PACT) - via an experimental medicine approach. Antipsychotics are the major therapeutic tool for chronic psychotic disorders, including schizophrenia, but do not significantly alter their course or real-life impact. Specific cognitive therapies achieve modest symptom reduction and improved function and cognition in psychosis patients, including "bottom-up" sensory-based targeted cognitive training (TCT). While benefits of TCT are evident at the group level, almost half of all patients demonstrate little or no cognitive gains after 30-40 hours (h) of TCT. For patients and clinicians, the costs and logistical complexities associated with these time- and resource-intensive interventions can be prohibitive. We propose and will test a novel "augmentation strategy" for using medications to specifically enhance the benefits of TCT in schizophrenia.
Read the detailed description
Subjects who meet criteria for study entry come to UCSD where consenting and a comprehensive screening and diagnostic assessment including a Mini-International Neuropsychiatric Interview are conducted. After initial screening, subjects return twice, approximately 7 days apart, for biomarker assessment after challenge with placebo (PBO) (Test 1) or amphetamine 5 mg po (AMPH) (Test 2). Subjects then enter the "treatment phase", completing up to 30 one-hour targeted cognitive training (TCT) sessions. Subjects are randomized to one of 2 groups: "AMPH Group" receive AMPH (5 mg po) 1h before each TCT session; "PBO Group" receive PBO dosed identically to AMPH. Pill identity (AMPH vs. PBO) is blind to subjects and staff.
TCT sessions are scheduled approximately 3 times each week for 10 weeks. TCT consists of 7 computerized exercises delivered on standardized laptops and headphones. Collectively, these exercises target learning mechanisms involving auditory perception and processing speed (Sound Sweeps, Fine Tuning) and auditory memory (Syllable Stacks, Memory Grid, To-Do List Training, Rhythm Recall, Hear-Hear). Training is structured into blocks that deliver stimulus sets with varying temporal and psychophysical parameters to allow continuous learning and improvement. Blocks consist of 10-35 adaptive trials where the subject's progression depends on their performance. Exercises apply an n-up/m-down algorithm to responses to estimate psychophysical thresholds while ensuring that participants remain engaged and challenged at an appropriate level (~80% accuracy) as their abilities improve.
Clinical and functional outcome measures are acquired at "baseline", and 1-2 days after completion of 10, 20 and 30 TCT sessions and 12 weeks post-training. Urine toxicology screens and Columbia Suicide Severity Rating Scales are performed at least weekly, prior to a TCT session. A treatment satisfaction scale (100 mm line) rates expectations at the start of the study and actual experience of treatment in three areas: "satisfaction", "hard work" and "worthwhile." Subjects from both groups return to UCSD 12 weeks after the TCT has ended, and outcome measures are reassessed to test the "durability" of benefits.
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- d-amphetamine, Placebo
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
d-amphetamineDrug
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.
PlaceboDrug
Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Subjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. Receives: Drug: Placebo |
| Active Drug | Active comparator | 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. Receives: Drug: d-amphetamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Clinical Outcome PANSS Total Score (PANSSt)
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.
Measured: approximately 10 weeks
Primary Functional Outcome WHODAS
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.
Measured: approximately 10 weeks
Primary Neurocognitive Outcome MCCB-C
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.
Measured: approximately 10 weeks
Secondary outcomes (5)
Secondary Clinical Outcome Measure PANSSp
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.
Measured: approximately 10 weeks
Secondary Clinical Outcome Measure PANSSn
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.
Measured: approximately 10 weeks
Psychotic Symptoms PSYRATS Hallucinations
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.
Measured: approximately 10 weeks
Manic Symptoms YMRS
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.
Measured: approximately 10 weeks
Current Depressive Symptoms PHQ
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.
Measured: approximately 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2020
- Study start9 Nov 2020
- Primary completion30 Dec 2024
- Study completion30 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Neal R. Swerdlow, M.D., Ph.D., University of California, San Diego
- Investigators
- Neal R Serdlow, M.D., Ph.D., Principal investigator, UC San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04414930
- Sponsor's protocol ID
- R33MH123603-01
- Status last verified
- Sep 2025
- First submitted
- 22 May 2020
- Last updated
- 17 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacologic Augmentation of Targeted Cognitive Training in Schizophrenia
- ClinicalTrials.gov ID
- NCT04414930
- Acronym / sponsor ID
- R33MH123603-01
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- 9 Nov 2020 (actual)
- Primary completion
- 30 Dec 2024 (actual)
- Study completion
- 30 Dec 2024 (actual)
- First posted
- 4 Jun 2020 (actual)
- Results
- Posted 17 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
These studies look to conduct efficient pilot testing of a novel intervention strategy for chronic psychotic disorders - Pharmacologic Augmentation of Cognitive Therapy (PACT) - via an experimental medicine approach. Antipsychotics are the major therapeutic tool for chronic psychotic disorders, including schizophrenia, but do not significantly alter their course or real-life impact. Specific cognitive therapies achieve modest symptom reduction and improved function and cognition in psychosis patients, including "bottom-up" sensory-based targeted cognitive training (TCT). While benefits of TCT are evident at the group level, almost half of all patients demonstrate little or no cognitive gains after 30-40 hours (h) of TCT. For patients and clinicians, the costs and logistical complexities associated with these time- and resource-intensive interventions can be prohibitive. We propose and will test a novel "augmentation strategy" for using medications to specifically enhance the benefits of TCT in schizophrenia.
Detailed description
Subjects who meet criteria for study entry come to UCSD where consenting and a comprehensive screening and diagnostic assessment including a Mini-International Neuropsychiatric Interview are conducted. After initial screening, subjects return twice, approximately 7 days apart, for biomarker assessment after challenge with placebo (PBO) (Test 1) or amphetamine 5 mg po (AMPH) (Test 2). Subjects then enter the "treatment phase", completing up to 30 one-hour targeted cognitive training (TCT) sessions. Subjects are randomized to one of 2 groups: "AMPH Group" receive AMPH (5 mg po) 1h before each TCT session; "PBO Group" receive PBO dosed identically to AMPH. Pill identity (AMPH vs. PBO) is blind to subjects and staff.
TCT sessions are scheduled approximately 3 times each week for 10 weeks. TCT consists of 7 computerized exercises delivered on standardized laptops and headphones. Collectively, these exercises target learning mechanisms involving auditory perception and processing speed (Sound Sweeps, Fine Tuning) and auditory memory (Syllable Stacks, Memory Grid, To-Do List Training, Rhythm Recall, Hear-Hear). Training is structured into blocks that deliver stimulus sets with varying temporal and psychophysical parameters to allow continuous learning and improvement. Blocks consist of 10-35 adaptive trials where the subject's progression depends on their performance. Exercises apply an n-up/m-down algorithm to responses to estimate psychophysical thresholds while ensuring that participants remain engaged and challenged at an appropriate level (~80% accuracy) as their abilities improve.
Clinical and functional outcome measures are acquired at "baseline", and 1-2 days after completion of 10, 20 and 30 TCT sessions and 12 weeks post-training. Urine toxicology screens and Columbia Suicide Severity Rating Scales are performed at least weekly, prior to a TCT session. A treatment satisfaction scale (100 mm line) rates expectations at the start of the study and actual experience of treatment in three areas: "satisfaction", "hard work" and "worthwhile." Subjects from both groups return to UCSD 12 weeks after the TCT has ended, and outcome measures are reassessed to test the "durability" of benefits.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboSubjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. |
| Active Drug | Active comparator | Drug: d-amphetamineSubjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- DSM-IV diagnosis of schizophrenia or schizoaffective disorder, depressed type
- Written informed consent to participate in the study
- Age 18 - 55
- Absence of dementia or mental retardation
- Urine toxicology negative for recreational drugs
Key exclusion criteria (5 listed)
- Meets DSM-IV criteria for current substance abuse or dependence and has been substance abstinent for less than 30 days
- A history of traumatic brain injury
- Auditory or visual impairments severe enough to prevent study participation
- Under conservatorship (determined by Anasazi)
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| d-amphetamineSubjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive amphetamine 5 mg po 1 hour prior to each training. | Drug | Active Drug |
| PlaceboSubjects complete 30 sessions of Targeted Cognitive Training (2-3 times per week), and receive placebo po 1 hour prior to each training. | Drug | Placebo |
Primary outcome
Primary Clinical Outcome PANSS Total Score (PANSSt)
Time frame: 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.
Primary Functional Outcome WHODAS
Time frame: 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.
Primary Neurocognitive Outcome MCCB-C
Time frame: 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.
5 secondary outcomes
Secondary Clinical Outcome Measure PANSSp
Time frame: approximately 10 weeks
Secondary Clinical Outcome Measure PANSSn
Time frame: approximately 10 weeks
Psychotic Symptoms PSYRATS Hallucinations
Time frame: approximately 10 weeks
Manic Symptoms YMRS
Time frame: approximately 10 weeks
Current Depressive Symptoms PHQ
Time frame: approximately 10 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neal R Serdlow, M.D., Ph.D. principal investigator
UC San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing d-amphetamine in people with Schizophrenia and Schizoaffective Disorder, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Clinical Outcome PANSS Total Score (PANSSt) (time frame: approximately 10 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.