Phase 2
N=82
Pharmacologically-augmented Cognitive Therapies (PACTs) for Schizophrenia.
Schizophrenia
Bottom Line
View on ClinicalTrials.gov: NCT02634684 ↗Enrolled (actual)
82
Serious AEs
0.0%
Results posted
Aug 2021
Primary outcome: Primary: Prepulse Inhibition (PPI) — 22.629; 41.162; 50.626; 50.626 % inhibition of startle
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Dextroamphetamine (Drug); Placebo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of California, San Diego
- Primary completion
- Aug 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Prepulse Inhibition (PPI) |
22.629; 41.162; 50.626; 50.626; 32.656; 39.545 | — |
| SECONDARY MATRICS Consensus Cognitive Battery Performance (MCCB) |
31.895; 39.895; 54.476; 57.870; 33.842; 38.105 | — |
| SECONDARY Targeted Cognitive Training (TCT): PositScience, Inc. |
-15.118; -50.158; 5.911; -2.113; 52.647; 101.000 | — |
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 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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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
- 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 160, Diastolic Blood Pressure 95
- Heart Rate 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)
Data sourced from ClinicalTrials.gov (NCT02634684). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.