SchizophreniaPhase 2NCT02634684
Pharmacologically-augmented Cognitive Therapies (PACTs) for Schizophrenia.
A Phase 2 study testing Dextroamphetamine in people with Schizophrenia, run by University of California, San Diego at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Dextroamphetamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2014to Aug 2020
- 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
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18-55 years old:
- Drug Free (No recreational/street drugs)
- Diagnosis of Schizophrenia or Schizoaffective Disorder, Depressed Type
- Must be stable on antipsychotic medication for at least 1 month
- Any medications other than antipsychotic medications need to be stable for at least 1 week
Who cannot join
- Dominant hand injury
- Hearing impairment at 40 dB
- Irregular menstrual cycle or cycle is no within in 25-35 days (menopausal is eligible)
- EKG, conduction abnormalities confirmed by cardiologist
- Reading component of Wide Range Achievement Test 4 (WRAT4) Score less than 70
- Any serious illness, including: Insulin-dependent diabetes, HIV, AIDS, cancer, stroke, heart attack, uncontrolled hypothyroidism
Show all 21Show fewer
- Sleep apnea
- A diagnosis of epilepsy or history of seizures with loss of consciousness
- Open/closed head injury with loss of consciousness greater than 1 minute at any time in the lifetime
- Blood pressure: Systolic Blood Pressure < 90 or > 160, Diastolic Blood Pressure < 45 or > 95
- Heart Rate < 55 or > 110
- Current use of Dexatrim or drugs containing phenylephrine (eligible if not used for at least 72 hours prior to participation)
- Current use of St. John's Wort, Milk Thistle (eligible if for at least 1 month)
- Self report of any illicit drug use within the last 30 days
- Positive urine toxicology
- Self-report of any use of ecstasy, lysergic acid diethylamide (LSD), mushrooms, gamma hydroxybutyrate (GHB), ketamine, phencyclidine (PCP), heroin or any intravenous-drugs within past year
- If there is a history of substance abuse/addiction, participant must be in remission for at least 6 months
- Within 1 month of recent psychiatric hospitalization
- Current mania
- Dementia/Alzheimer's diagnosis
- Mania episode meeting criteria outlined in the MINI-International Neuropsychiatric Interview Plus 6.0 (M.I.N.I. plus 6.0) anytime in the lifetime (hypomania/Bipolar II eligible)
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
Official title: Pharmacologic Augmentation of Neurocognition and Cognitive Training in Psychosis
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.
Read the detailed description
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:
- PPI
- neurocognition (MCCB performance)
- computerized TCT performance in biomarker-identified SZ/SZA patients.
- The 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.
- Conditions
- Schizophrenia
- Being tested
- Dextroamphetamine, Placebo
- Keywords
- Schizophrenia, Schizoaffective Disorder, Mental Disorders, Anti-Dyskinesia Agents, Antiparkinson Agents, Central Nervous System Agents, Dopamine Agents, Excitatory Amino Acid Agents, Excitatory Amino Acid Antagonists, Molecular Mechanisms of Pharmacological Action, Neurotransmitter Agents, Pharmacologic Actions, Physiological Effects of Drugs, Therapeutic Uses, Prepulse inhibition, Neurocognition, Working memory, Dextroamphetamine, MATRICS Consensus Cognitive Battery, Pharmacologic Augmentation of Cognitive Therapies
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DextroamphetamineDrug
Also called d-amphetamine, Dexedrine
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Dextroamphetamine; Drug: Placebo |
| 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. Receives: Drug: Dextroamphetamine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: two visits, 1 week apart, each visit lasting approximately 6 hours
Secondary outcomes (2)
MATRICS Consensus Cognitive Battery Performance (MCCB)
The T-score indicates the performance on a neurocognitive battery of tests. Higher score reflects better performance.
Measured: two visits, 1 week apart, each visit lasting approximately 6 hours
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.
Measured: two visits, 1 week apart, each visit lasting approximately 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2015 (estimated)
- Study start1 Jul 2014
- Primary completionAug 2020
- Study completionAug 2020
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.
- Publications (32)Papers the sponsor has linked to this study.
- 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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 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. Swerdlow, M.D., Ph.D., Principal investigator, UC San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02634684
- Sponsor's protocol ID
- 5R01MH059803-15
- Other IDs
- Eyeblink Study
- Status last verified
- Aug 2021
- First submitted
- 14 Dec 2015
- Last updated
- 17 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 22157876Barch 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.
PubMed 16005384Fisher M, Holland C, Merzenich MM, Vinogradov S. Using neuroplasticity-based auditory training to improve verbal memory in schizophrenia. Am J Psychiatry. 2009 Jul;166(7):805-11. doi: 10.1176/appi.ajp.2009.08050757. Epub 2009 May 15.
PubMed 19448187Fisher M, Holland C, Subramaniam K, Vinogradov S. Neuroplasticity-based cognitive training in schizophrenia: an interim report on the effects 6 months later. Schizophr Bull. 2010 Jul;36(4):869-79. doi: 10.1093/schbul/sbn170. Epub 2009 Mar 5.
PubMed 19269924Tarasenko M, Perez VB, Pianka ST, Vinogradov S, Braff DL, Swerdlow NR, Light GA. Measuring the capacity for auditory system plasticity: An examination of performance gains during initial exposure to auditory-targeted cognitive training in schizophrenia. Schizophr Res. 2016 Apr;172(1-3):123-30. doi: 10.1016/j.schres.2016.01.019. Epub 2016 Feb 2.
PubMed 26851143Vinogradov S, Fisher M, de Villers-Sidani E. Cognitive training for impaired neural systems in neuropsychiatric illness. Neuropsychopharmacology. 2012 Jan;37(1):43-76. doi: 10.1038/npp.2011.251. Epub 2011 Nov 2.
PubMed 22048465Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Mahmoud RA, Kirshner MA, Sorisio DA, Bies RR, Gharabawi G. Anticholinergic activity of 107 medications commonly used by older adults. J Am Geriatr Soc. 2008 Jul;56(7):1333-41. doi: 10.1111/j.1532-5415.2008.01737.x. Epub 2008 May 26.
PubMed 18510583Chou HH, Talledo JA, Lamb SN, Thompson WK, Swerdlow NR. Amphetamine effects on MATRICS Consensus Cognitive Battery performance in healthy adults. Psychopharmacology (Berl). 2013 May;227(1):165-76. doi: 10.1007/s00213-012-2948-x. Epub 2013 Jan 12.
PubMed 23314393Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005 Sep 22;353(12):1209-23. doi: 10.1056/NEJMoa051688. Epub 2005 Sep 19.
PubMed 16172203Dinse HR, Ragert P, Pleger B, Schwenkreis P, Tegenthoff M. Pharmacological modulation of perceptual learning and associated cortical reorganization. Science. 2003 Jul 4;301(5629):91-4. doi: 10.1126/science.1085423.
PubMed 12843392Goldberg TE, Bigelow LB, Weinberger DR, Daniel DG, Kleinman JE. Cognitive and behavioral effects of the coadministration of dextroamphetamine and haloperidol in schizophrenia. Am J Psychiatry. 1991 Jan;148(1):78-84. doi: 10.1176/ajp.148.1.78.
PubMed 1984711Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996 Mar;153(3):321-30. doi: 10.1176/ajp.153.3.321.
PubMed 8610818Green MF, Kern RS, Heaton RK. Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS. Schizophr Res. 2004 Dec 15;72(1):41-51. doi: 10.1016/j.schres.2004.09.009.
PubMed 15531406Hamidovic A, Dlugos A, Palmer AA, de Wit H. Catechol-O-methyltransferase val158met genotype modulates sustained attention in both the drug-free state and in response to amphetamine. Psychiatr Genet. 2010 Jun;20(3):85-92. doi: 10.1097/YPG.0b013e32833a1f3c.
PubMed 20414144Hamidovic A, Dlugos A, Palmer AA, de Wit H. Polymorphisms in dopamine transporter (SLC6A3) are associated with stimulant effects of D-amphetamine: an exploratory pharmacogenetic study using healthy volunteers. Behav Genet. 2010 Mar;40(2):255-61. doi: 10.1007/s10519-009-9331-7. Epub 2010 Jan 21.
PubMed 20091113
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacologic Augmentation of Neurocognition and Cognitive Training in Psychosis
- ClinicalTrials.gov ID
- NCT02634684
- Acronym / sponsor ID
- 5R01MH059803-15
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Schizoaffective Disorder, Mental Disorders, Anti-Dyskinesia Agents, Antiparkinson Agents, Central Nervous System Agents, Dopamine Agents, Excitatory Amino Acid Agents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- 1 Jul 2014 (actual)
- Primary completion
- Aug 2020 (actual)
- Study completion
- Aug 2020 (actual)
- First posted
- 18 Dec 2015 (estimated)
- Results
- Posted 16 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- PPI
- neurocognition (MCCB performance)
- computerized TCT performance in biomarker-identified SZ/SZA patients.
- The 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| dextroamphetamine | Active comparator | Drug: Dextroamphetamine, Drug: PlaceboDrug: 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: Dextroamphetamine, Drug: PlaceboDrug: 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 18-55 years old:
- Drug Free (No recreational/street drugs)
- Diagnosis of Schizophrenia or Schizoaffective Disorder, Depressed Type
- Must be stable on antipsychotic medication for at least 1 month
- Any medications other than antipsychotic medications need to be stable for at least 1 week
Key exclusion criteria (21 listed)
- Dominant hand injury
- Hearing impairment at 40 dB
- Irregular menstrual cycle or cycle is no within in 25-35 days (menopausal is eligible)
- EKG, conduction abnormalities confirmed by cardiologist
- Reading component of Wide Range Achievement Test 4 (WRAT4) Score less than 70
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 |
|---|---|---|
| DextroamphetamineAlso: d-amphetamine, DexedrineEach 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. | Drug | Placebo, dextroamphetamine |
| PlaceboEach 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. | Drug | Placebo, dextroamphetamine |
Primary outcome
Prepulse Inhibition (PPI)
Time frame: two visits, 1 week apart, each visit lasting approximately 6 hours
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.
2 secondary outcomes
MATRICS Consensus Cognitive Battery Performance (MCCB)
Time frame: two visits, 1 week apart, each visit lasting approximately 6 hours
Targeted Cognitive Training (TCT): PositScience, Inc.
Time frame: two visits, 1 week apart, each visit lasting approximately 6 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22157876Swerdlow 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.
- Background: PubMed 16005384Barch 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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- Background: PubMed 26851143Tarasenko M, Perez VB, Pianka ST, Vinogradov S, Braff DL, Swerdlow NR, Light GA. Measuring the capacity for auditory system plasticity: An examination of performance gains during initial exposure to auditory-targeted cognitive training in schizophrenia. Schizophr Res. 2016 Apr;172(1-3):123-30. doi: 10.1016/j.schres.2016.01.019. Epub 2016 Feb 2.
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- Individual participant dataSharing planned: No
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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. Swerdlow, 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 Dextroamphetamine in people with Schizophrenia, 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 5 inclusion and 21 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 Aug 2021. 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 16 Aug 2021). 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?
Prepulse Inhibition (PPI) (time frame: two visits, 1 week apart, each visit lasting approximately 6 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02634684, which also lists 32 linked publications.
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 Aug 2021.