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| ID | Type | Description | Link |
|---|---|---|---|
| Eyeblink Study | Other Identifier | UC San Diego |
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This application seeks renewed support for MH59803, "Dopaminergic substrates of startle gating across species," to extend a clear path of "bench-to-bedside" progress towards a critical paradigm shift in therapeutic models for schizophrenia (SZ) and schizoaffective disorder, depressed type (SZA): the use of Pharmacologic Augmentation of Cognitive Therapies (PACTs). This novel therapeutic strategy for SZ/SZA directly addresses the need for more effective treatments for this devastating disorder. MH59803 has investigated the neural regulation of laboratory-based measures of deficient information processing in SZ/SZA patients, using rodents and healthy human subjects (HS) to explicate the biology of these deficits, and to establish a rational basis for developing novel therapies for SZ/SZA. In its first 9 years, MH59803 studies of the neural regulation of prepulse inhibition (PPI) of startle in rats focused on basic neurobiological and molecular mechanisms. Over the past 2 years of support, MH59803 studies moved "from bench-to-bedside," focusing on dopamine (DA) agonist effects on PPI and neurocognition in HS, and their regulation by genes identified in cross-species studies. These studies detected biological markers that predict PPI-enhancing and pro-cognitive effects of the DA releaser, amphetamine (AMPH) in humans, leading to specific predictions of AMPH effects on PPI, neurocognition and Targeted Cognitive Training in SZ/SZA patients. If confirmed in the present application, these predictions could help transform therapeutic approaches to SZ/SZA. This renewal application of MH59803 thus reflects a logical progression of studies at systems and molecular levels, translated first to HS, and now to potentially transformative therapeutic models in SZ/SZA patients.
MH59803 demonstrated that AMPH (20 mg p.o.) significantly increased PPI and neurocognitive performance (MATRICS Consensus Cognitive Battery; MCCB) in HS characterized by specific performance-based or genetic biomarkers, including the val/val genotype for the rs4680 polymorphism of catechol-O-methyltransferase (COMT). Mechanistically-informative results were detected in studies of AMPH effects on PPI in rats with high vs. low brain regional Comt expression. Together with several reports of improved neurocognition and no adverse effects of acute or sustained AMPH administration to antipsychotic (AP)-medicated SZ/SZA patients, MH59803 findings provide a strong rationale for the next goal of this application: to test the potential utility of AMPH in a paradigm of biomarker-informed "PACTs". This "next step" is highly innovative - never previously reported, or perhaps even attempted - and consistent with National Institute of Mental Health (NIMH) objectives, directly challenges existing models for SZ/SZA therapeutics. Investigators will determine whether a test dose of 10 mg AMPH p.o. administered to biomarker-identified, AP-medicated SZ/SZA patients generates predicted increases in PPI, MCCB performance, and sensory discrimination learning in a Targeted Cognitive Training (TCT) module. In total, Investigators will leverage knowledge generated through converging cross-species studies in MH59803, to directly advance scientific and clinical domains, by testing the effects of a pro-cognitive drug on neurophysiological and neurocognitive performance, and Targeted Cognitive Training, in biomarker-stratified subgroups of SZ/SZA patients.
Aim: To assess acute effects of AMPH (0 vs 10 mg po) on PPI, neurocognition and computerized TCT in AP-medicated SZ/SZA patients. Hypothesis: PPI- and MCCB-enhancing effects of AMPH seen previously in HS will also be detected in SZ/SZA patients, as will TCT-enhancing effects of AMPH. Prediction: In a within-subject, placebo-controlled, randomized design, AMPH (10 mg po) will increase PPI and enhance MCCB and TCT performance in medicated SZ/SZA patients, particularly among those characterized by low basal performance levels and/or the val/val rs4680 COMT polymorphism. Concurrent HS testing will confirm and extend findings of AMPH effects on PPI and neurocognition, and help interpret findings in SZ/SZA patients.
In all participants, the aim to assess acute effects of 0 vs. 10 mg po dextroamphetamine (AMPH) on Prepulse Inhibition (PPI), neurocognition MATRICS: Consensus Cognitive Battery; MCCB, and computerized Targeted Cognitive Training (TCT).
Hypothesis: AMPH will enhance:
Prediction: In a within-subject, placebo-controlled, randomized design, AMPH (10 mg po) will increase PPI and enhance MCCB and TCT performance in medicated SZ/SZA patients, particularly among those characterized by low basal performance levels and/or the val/val rs4680 COMT polymorphism. Concurrent HS testing will confirm and extend findings of AMPH effects on PPI and neurocognition, and help interpret findings in SZ/SZA patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| dextroamphetamine | Active Comparator | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) 30 minutes after arriving at the lab. The participant then completes approximately 6 hours of testing in the laboratory. The participant stays at the lab for 7.5 hours in order to monitor physical condition in case the participant received the active pill One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
|
| Placebo | Placebo Comparator | Drug: Dexedrine, dextroamphetamine, d-amphetamine Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) 30 minutes after arriving at the lab. The participant then completes approximately 6 hours of testing in the laboratory. The participant stays at the lab for 7.5 hours in order to monitor physical condition in case the participant received the active pill One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dextroamphetamine | Drug | Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| Measure | Description | Time Frame |
|---|---|---|
| Prepulse Inhibition (PPI) | PPI was assessed with 42 trials of 6 types: 118 dB 40 ms pulse alone (P) & the same P preceded 10, 20, 30, 60, or 120 ms by a prepulse (pp) 16 dB over background. Startle magnitude (SM), habituation, latency & latency facilitation were measured to interpret changes in PPI. %PPI = 100 x [(SM on P trials) - (SM on pp+P trials)] / SM on P trials. Example: SM on P trials = 80 units SM on pp+P trials = 30 units %PPI = 100 x (80-30)/80 = 100 x 50/80 = 62.5% Greater %PPI mean the reflex has been inhibited to a greater extent in the presence of a pp. %PPI can't exceed 100: when SM on pp+P trials = 0, then %PPI = 100 x (SM on P trials - 0)/SM on P trials = 100 x 1 = 100%. However, %PPI can theoretically be infinitely negative since SM on pp+P trials could be infinitely large ("prepulse facilitiation" (PPF)), i.e. SM is potentiated in the presence of a pp. PPF is "normal" at very short & very long pp intervals, but not within a species-specific physiological range of intervals. | two visits, 1 week apart, each visit lasting approximately 6 hours |
| Measure | Description | Time Frame |
|---|---|---|
| MATRICS Consensus Cognitive Battery Performance (MCCB) | The T-score indicates the performance on a neurocognitive battery of tests. Higher score reflects better performance. | two visits, 1 week apart, each visit lasting approximately 6 hours |
| Targeted Cognitive Training (TCT): PositScience, Inc. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Neal R. Swerdlow, M.D., Ph.D. | UC San Diego | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Teaching Facility (CTF-B102) at UCSD Medical Center | San Diego | California | 92103 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22157876 | Background | Swerdlow NR. Beyond antipsychotics: pharmacologically-augmented cognitive therapies (PACTs) for schizophrenia. Neuropsychopharmacology. 2012 Jan;37(1):310-1. doi: 10.1038/npp.2011.195. No abstract available. | |
| 16005384 | Background | Barch DM, Carter CS. Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers. Schizophr Res. 2005 Sep 1;77(1):43-58. doi: 10.1016/j.schres.2004.12.019. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Subjects With Schizophrenia: Placebo 1st, Then 10 mg Amphetamine | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| FG001 | Subjects With Schizophrenia: 10 mg Amphetamine 1st, Then Placebo | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| FG002 | Healthy Subjects: Placebo 1st, Then 10 mg Amphetamine | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| FG003 | Healthy Subjects: 10 mg Amphetamine 1st, Then Placebo | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Subjects With Schizophrenia: Placebo 1st, Then 10 mg Amphetamine | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Prepulse Inhibition (PPI) | PPI was assessed with 42 trials of 6 types: 118 dB 40 ms pulse alone (P) & the same P preceded 10, 20, 30, 60, or 120 ms by a prepulse (pp) 16 dB over background. Startle magnitude (SM), habituation, latency & latency facilitation were measured to interpret changes in PPI. %PPI = 100 x [(SM on P trials) - (SM on pp+P trials)] / SM on P trials. Example: SM on P trials = 80 units SM on pp+P trials = 30 units %PPI = 100 x (80-30)/80 = 100 x 50/80 = 62.5% Greater %PPI mean the reflex has been inhibited to a greater extent in the presence of a pp. %PPI can't exceed 100: when SM on pp+P trials = 0, then %PPI = 100 x (SM on P trials - 0)/SM on P trials = 100 x 1 = 100%. However, %PPI can theoretically be infinitely negative since SM on pp+P trials could be infinitely large ("prepulse facilitiation" (PPF)), i.e. SM is potentiated in the presence of a pp. PPF is "normal" at very short & very long pp intervals, but not within a species-specific physiological range of intervals. | Posted | Mean | Standard Deviation | % inhibition of startle | two visits, 1 week apart, each visit lasting approximately 6 hours |
|
two visits, 1 week apart, each visit lasting approximately 6 hours
Each subject received both interventions (placebo (PBO) and 10 mg amphetamine (AMPH)) separated by 1 week (wk), with pill order (PBO wk 1, AMPH wk 2 vs. AMPH wk 1, PBO wk 2) balanced. The 2 groups were "Subjects with schizophrenia" (SZ) and "healthy subjects"(HS). Assuming that adverse effects are independent of test order, there are 4 possible Arms/Groups; adverse events across these 4 Arms/Groups were:
SZ: AMPH = 0 SZ: PBO = 0 HS: AMPH = 0 HS: PBO = 0
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Subjects With Schizophrenia: Placebo | Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Neal Swerdlow, M.D., Ph.D. | UC San Diego | 619-543-6270 | nswerdlow@health.ucsd.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 9, 2020 | Jun 7, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 9, 2020 | Jun 7, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| D001523 | Mental Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
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| ID | Term |
|---|---|
| D003913 | Dextroamphetamine |
| ID | Term |
|---|---|
| D000661 | Amphetamine |
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
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|
| Placebo | Drug | Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
|
Auditory discrimination learning: Subjects identify direction (up vs. down) of 2 consecutive sound sweeps. Parameters (e.g. inter-sweep interval, sweep duration) are established for subjects to maintain 80% correct responses. On screen and test days, subjects complete 1h of TCT. Analytic software yields the key measures: auditory processing speed (APS) and APS "learning". APS is the shortest inter-stimulus interval at which a subject performs to criteria and APS learning is the difference (ms) between the first APS and the best APS of the subsequent trials. A smaller APS reflects "better" discrimination (i.e., subject correctly identified frequency "sweep" direction despite a smaller ms gap between stimuli) and a larger ms value for APS learning reflects more learning, i.e., faster APS with repeated trials. Limits for APS are capped at 0-to-1000 ms; values for APS learning are capped at (-) 1000-to-APS. |
| two visits, 1 week apart, each visit lasting approximately 6 hours |
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| 26062785 | Background | Swerdlow NR, Bhakta S, Chou HH, Talledo JA, Balvaneda B, Light GA. Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis. Neuropsychopharmacology. 2016 Jan;41(2):419-30. doi: 10.1038/npp.2015.162. Epub 2015 Jun 11. |
| 24405980 | Background | Swerdlow NR, Light GA, Sprock J, Calkins ME, Green MF, Greenwood TA, Gur RE, Gur RC, Lazzeroni LC, Nuechterlein KH, Radant AD, Ray A, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Sugar CA, Tsuang DW, Tsuang MT, Turetsky BI, Braff DL. Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS. Schizophr Res. 2014 Feb;152(2-3):503-12. doi: 10.1016/j.schres.2013.12.004. Epub 2014 Jan 7. |
| 19148623 | Background | Talledo JA, Sutherland Owens AN, Schortinghuis T, Swerdlow NR. Amphetamine effects on startle gating in normal women and female rats. Psychopharmacology (Berl). 2009 May;204(1):165-75. doi: 10.1007/s00213-008-1446-7. Epub 2009 Jan 16. |
| 17135482 | Background | Turetsky BI, Calkins ME, Light GA, Olincy A, Radant AD, Swerdlow NR. Neurophysiological endophenotypes of schizophrenia: the viability of selected candidate measures. Schizophr Bull. 2007 Jan;33(1):69-94. doi: 10.1093/schbul/sbl060. Epub 2006 Nov 29. |
| Background | Wilkinson GS, Robertson GJ (2006) WRAT4: Wide Range Achievement Test professional manual, 4th edn Psychological Assessment Resources: Lutz, FL |
| BG001 | Subjects With Schizophrenia: 10 mg Amphetamine 1st, Then Placebo | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| BG002 | Healthy Subjects: Placebo 1st, Then 10 mg Amphetamine | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| BG003 | Healthy Subjects: 10 mg Amphetamine 1st, Then Placebo | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| BG004 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| OG000 | Subjects With Schizophrenia: Placebo 1st, Then 10 mg Amphetamine | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| OG001 | Subjects With Schizophrenia: 10 mg Amphetamine 1st, Then Placebo | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| OG002 | Healthy Subjects: Placebo 1st, Then 10 mg Amphetamine | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
| OG003 | Healthy Subjects: 10 mg Amphetamine 1st, Then Placebo | Drug: Dexedrine, dextroamphetamine, d-amphetamine. Dosage form, frequency and duration: Each participant receives a single pill of placebo or active drug (dextroamphetamine) 30 minutes after arriving at the lab. The participant then completes ~6 hours of testing in the laboratory. The participant stays at the lab for ~7.5 hours to monitor physical condition in case the participant received the active pill. One week later, the participant receives a single pill of comparator and is again tested in the laboratory. Total of 1 visits, approximately 1 week apart; in total, each participant receives one placebo pill and 1 active pill separated by one week. Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. |
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| Secondary | MATRICS Consensus Cognitive Battery Performance (MCCB) | The T-score indicates the performance on a neurocognitive battery of tests. Higher score reflects better performance. | Posted | Mean | Standard Deviation | standardized T-score | two visits, 1 week apart, each visit lasting approximately 6 hours |
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| Secondary | Targeted Cognitive Training (TCT): PositScience, Inc. | Auditory discrimination learning: Subjects identify direction (up vs. down) of 2 consecutive sound sweeps. Parameters (e.g. inter-sweep interval, sweep duration) are established for subjects to maintain 80% correct responses. On screen and test days, subjects complete 1h of TCT. Analytic software yields the key measures: auditory processing speed (APS) and APS "learning". APS is the shortest inter-stimulus interval at which a subject performs to criteria and APS learning is the difference (ms) between the first APS and the best APS of the subsequent trials. A smaller APS reflects "better" discrimination (i.e., subject correctly identified frequency "sweep" direction despite a smaller ms gap between stimuli) and a larger ms value for APS learning reflects more learning, i.e., faster APS with repeated trials. Limits for APS are capped at 0-to-1000 ms; values for APS learning are capped at (-) 1000-to-APS. | Posted | Mean | Standard Deviation | msec | two visits, 1 week apart, each visit lasting approximately 6 hours |
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| 0 |
| 38 |
| 0 |
| 38 |
| 0 |
| 38 |
| EG001 | Subjects With Schizophrenia: 10 mg Amphetamine | Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. | 0 | 38 | 0 | 38 | 0 | 38 |
| EG002 | Healthy Subjects: Placebo | Placebo: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. | 0 | 44 | 0 | 44 | 0 | 44 |
| EG003 | Healthy Subjects: 10 mg Amphetamine | Dextroamphetamine: Each participant receives a single pill of placebo or active drug (dextroamphetamine 10 mg) and completes approximately 6 hours of testing in the laboratory. One week later, that participant receives a single pill of the alternate comparator and is again tested in the laboratory. Thus, in total, each participant receives one placebo pill and one active pill, separated by one week. | 0 | 44 | 0 | 44 | 0 | 44 |
Not provided
Not provided
| D000588 |
| Amines |
| D009930 | Organic Chemicals |
| amphetamine |
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| amphetamine |
|