Clinical High Risk for Psychosis (CHR)
Conditions
Brief summary
The goal of this clinical trial is to learn how tests undertaken by people at high risk of developing psychosis (aged 17 to 30 years old) change when those people are given the study drug MT1988 daily for 8 weeks. This will help identify tests that could be used in later trials developing treatments for symptoms in people at high risk of developing psychosis, to measure whether those new treatments are effective. The main question this trial aims to answer is: Can any of the tests (biomarkers) used in this study detect changes in participants dosed with one of two different dose levels of MT1988? Researchers will compare the results from two dose levels of MT1988 to a placebo group. Researchers do not expect to see the test results change in participants taking placebo and this will be compared to changes expected in test results in participants taking MT1988. Participants will: * take a dose of MT1988 or placebo twice per day for 8 weeks * attend clinic appointments every two weeks to undertake assessments * report any side effects they experience to the researchers
Interventions
DRUGMT1988 Low Dose
Oral dosing MT1988; dose level 1
DRUGMT1988 High Dose
Oral dosing MT1988; dose level 2
DRUGPlacebo
Oral Placebo; blinded to match MT1988 all doses
Sponsors
Monument Therapeutics Limited
National Institute of Mental Health (NIMH)
Foundation for the National Institutes of Health
Accelerating Medicines Partnership (AMP)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
17 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* Aged 17 to 30 years at time of consent. * Capacity to provide informed consent. (For patients under 17 years, participants must assent and informed consent provided by one parent or legal guardian). * Meet diagnostic criteria for Clinical High Risk of Psychosis (CHR). * For females of reproductive potential - not pregnant or nursing and willing to comply with contraceptive requirements.
Exclusion criteria
* Clinically significant medical disorder or laboratory test abnormality at Day 1. * History of or current condition which may prevent participant from complying with study procedures. * Past or current schizophrenia, other disorder with symptoms of psychosis, major cognitive disorder resulting from traumatic brain injury. * Received antipsychotic medication equivalent to a total lifetime haloperidol dose \>50 mg. * Current use of medications which could interfere with the study endpoints - to be assessed by the Investigator at screening. * Unable to abstain from nicotine (e.g. cigarettes, vape) for two hours before cognitive testing. * Unable to abstain from marijuana use on test day prior to test completion. * History of suicide attempt or behavior in previous 12 months, or risk of suicidal behavior during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to week 8 in test of verbal memory (List Learning Task) as measured by the Penn Computerized Neurobehavioral Battery (PennCNB) test battery | Day 56 | — |
| Change from baseline to week 8 in attenuated positive symptoms as measured by PSYCHS-CT total score | Day 56 | PSYCHS-CT: Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States (CAARMS) Harmonized with the Structured Interview for Pyschosis-risk Syndromes (SIPS) - Clinical Trials version. Total score of 0-90 across maximum 15 domain; where a higher score indicates more severe symptoms |
| Change from baseline to week 8 in negative symptoms as measured by the Negative Symptom Inventory - Psychosis Risk (NSI-PR) total score | Day 56 | Total score of 0-44 across 11 domains; where a higher score indicates more severe symptoms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety & tolerability as measured by number of treatment related adverse events | Day 1 to Day 84 | The total number of treatment related adverse events reported per study arm (high dose MT1988, low dose MT1988, placebo) will be compared |
| Safety & tolerability as measured by proportion of participants with treatment related adverse events | Day 1 to Day 84 | The proportion of participants in each study arm (high dose MT1988, low dose MT1988, placebo) experiencing treatment related adverse events will be compared |
| Change from baseline to week 4 in test of verbal memory (List learning task) as measured by PennCNB battery | Day 28 | — |
| Change from baseline to weeks 4 and 8 in overall composite score of cognitive performance as measured by PennCNB test battery | Day 28 and Day 56 | Composite includes Continuous Performance Test, Fractal N-Back, Digit-Symbol Substitution Test, Digit Symbol Recall, Visual Object Learning Test, Emotion Recognition Test, Finger Tapping Test, Motor Praxis |
| Change from baseline to weeks 4 and 8 in a cognitive test of working memory and executive function as measured by CANTAB SWM test. | Day 28 and Day 56 | — |
| Change from baseline to weeks 4 and 8 in a cognitive test of sustained attention as measured by CANTAB RVP test. | Day 28 and Day 56 | — |
| Change from baseline to weeks 4 and 8 in neurophysiology (EEG) as measured by mismatch negativity; auditory oddball P300. | Day 28 and Day 56 | — |
| Change from baseline to week 4 in attenuated positive symptoms, as measured by the PSYCHS-CT total score. | Day 28 | PSYCHS-CT: Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States (CAARMS) Harmonized with the Structured Interview for Pyschosis-risk Syndromes (SIPS) - Clinical Trials version. Total score of 0-90 across maximum 15 domain; where a higher score indicates more severe symptoms |
| Change from baseline to week 4 in negative symptoms as measured by the NSI-PR total score. | Day 28 | Total score of 0-44 across 11 domains; where a higher score indicates more severe symptoms |
| Change from baseline to weeks 4 and 8 in overall psychopathology as measured by the Positive And Negative Symptoms Scale (PANSS) total score. | Day 28 and Day 56 | Total PANSS score between 30 and 120; where a higher score indicates more severe symptoms |
| Change from baseline to weeks 4 and 8 in symptoms of anxiety as measured by the Overall Anxiety Severity and Impairment Scale (OASIS). | Day 28 and Day 56 | The OASIS (Overall Anxiety Severity and Impairment Scale) ranges from 0 to 20. Higher scores indicate greater severity and impairment due to anxiety symptoms. |
| Change from baseline to weeks 4 and 8 in symptoms of depression as measured by the Calgary Depression Scale for Schizophrenia (CDSS). | Day 28 and Day 56 | The Calgary Depression Scale for Schizophrenia (CDSS) ranges from 0 to 27. Higher scores indicate more severe depressive symptoms in individuals with schizophrenia. |
| Change from baseline to weeks 4 and 8 in symptoms of stress as measured by the Perceived Stress Scale (PSS). | Day 28 and Day 56 | The Perceived Stress Scale (PSS) ranges from 0 to 40. Higher scores indicate greater levels of perceived stress |
| Change from baseline to weeks 4 and 8 in sleep disturbance as measured by the Patient-Reported Outcomes Measurement Information System - Sleep Disturbance (PROMIS-SD). | Day 28 and Day 56 | The PROMIS-SD scale ranges from 8 to 40. Higher scores indicate greater severity of recent sleep disturbance. |
| Change from baseline to week 8 in biospecimen assays (levels of inflammation) as measured by blood samples (ELISA). | Day 56 | — |
| Change from baseline to week 8 in cortisol levels, indicative of stress response, as measured by saliva collection (ELISA). | Day 56 | — |
| Change from baseline to week 8 in physical/sedentary behavior as measured by a phone accelerometer and assessed by the mindLAMP app | Day -7 to Day 56 | — |
| Change from baseline to week 8 in roaming/movement behavior as measured by a phone GPS and assessed by the mindLAMP app | Day -7 to Day 56 | — |
| Change from baseline to week 8 in screen state (screen on/off timestamps) assessed by the mindLAMP app | Day -7 to Day 56 | — |
| Correlation between latent inhibition score and cognitive change from baseline to weeks 4 and 8 as measured by CANTAB SWM. | Day 28 and Day 56 | The data will be explored to determine whether the score on the latent inhibition assessment tool ("positive", "negative") correlates with cognitive change from baseline to weeks 4 and 8 as measured by CANTAB SWM, using Pearson's correlation coefficient. |
| Correlation between latent inhibition score and cognitive change from baseline to weeks 4 and 8 as measured by CANTAB RVP. | Day 28 and Day 56 | The data will be explored to determine whether the score on the latent inhibition assessment tool ("positive", "negative") correlates with cognitive change from baseline to weeks 4 and 8 as measured by CANTAB RVP, using Pearson's correlation coefficient. |
| Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and PennCNB score change at week 8. | Day 56 | Polygenic risk scores serve to modestly improve psychosis risk prediction. The data will be examined for correlation between individual genetic risk prediction for psychosis and any changes between baseline and Day 56 for each individual biomarker, using Pearson's correlation coefficient. |
| Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and PYSCHS-CT score change at week 8. | Day 56 | Polygenic risk scores serve to modestly improve psychosis risk prediction. The data will be examined for correlation between individual genetic risk prediction for psychosis and any changes between baseline and Day 56 for each individual biomarker, using Pearson's correlation coefficient. |
| Correlation between the polygenic risk score (as measured by plasma isolated-DNA samples) and NSI-PR score change at week 8. | Day 56 | Polygenic risk scores serve to modestly improve psychosis risk prediction. The data will be examined for correlation between individual genetic risk prediction for psychosis and any changes between baseline and Day 56 for each individual biomarker, using Pearson's correlation coefficient. |
Countries
United States
Contacts
CONTACTSheryl Caswell
PRINCIPAL_INVESTIGATORScott Woods, M.D.
Yale University of Medicine
PRINCIPAL_INVESTIGATORMartha E Shenton, PhD
Massachusetts General Brigham
Outcome results
None listed