Parkinson Disease Psychosis
Conditions
Brief summary
This clinical trial will test whether AGB101 (low-dose levetiracetam, 220 mg, extended release tablet) can improve symptoms of psychosis in Parkinson's disease. Participants will be asked to complete up to 5 in-person study visits over approximately 20 weeks. Participants will receive both AGB101 and a placebo to take once a day for 6 weeks, with a 4-week washout in between. Participation will also involve physical/neurological exams, questionnaires, paper and pencil tests, providing blood and urine samples, and completing two MRI exams.
Detailed description
Hallucinations and memory impairment have a parallel clinical course in Parkinson's disease (PD) and are independently associated dysfunction and pathology accumulation in hippocampal subregions. Similar alterations of hippocampal function are found in schizophrenic patients with memory impairment and positive psychotic symptoms. These findings suggest that dysfunction of the hippocampus may be a shared mechanism for memory impairment and psychosis across diseases. This investigation aims to address these questions and assess the efficacy of AGB101 for the treatment of psychosis in PD.
Interventions
DRUGAGB101
low-dose levetiracetam, 220 mg, extended release tablet
Sponsors
Johns Hopkins University
AgeneBio
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following inclusion criteria at screening: 1. Subjects between 40 and 85 years old (inclusive) in good general health: 1. Willing and able to consent and participate for the duration of the study. 2. Have eighth-grade education or good work history sufficient to exclude mental retardation. 3. Have visual and auditory acuity adequate for neuropsychological testing. 4. Have proficient fluency of the native local language to participate in all the neuropsychological test assessments. 2. Have a study partner who has sufficient contact (≥ 2 hours per week) with the subject to assist with dosing of study medication (if necessary) and provide assessments of any changes and an independent evaluation of the subject's functioning. 3. Have PDP as defined by all of the following criteria and consistent with the National Institute of Neurological Disorders and Stroke/National Institute of Mental Health (NINDS/NIMH) criteria: 1. Meets United Kingdom brain bank criteria for PD 2. Presence of at least one of the following symptoms * Illusions * False sense of presence * Hallucinations * Delusions 3. The symptoms of Criterion b occur after the onset of PD. 4. The symptoms of Criterion b are recurrent or continuous for 1 month. 5. The symptoms of Criterion b are not better accounted for by another cause of Parkinsonism such as dementia with Lewy bodies, psychiatric disorders such as schizophrenia, schizoaffective disorder, delusional disorder, or mood disorder with psychotic features, or a general medical condition including delirium. 6. May have the following associated features: * With/without insight * With/without dementia * With/without treatment for PD 4. Patients must be experiencing symptom(s) of Criterion 3b at least once a week during the 4 weeks prior to the screening visit. 5. Patients being treated for symptom(s) of Criterion 3b must be off medication for at least 2 weeks prior to randomization. 6. Patients must be on a stable regimen of medication for PD for at least 4 weeks prior to randomization. 7. Permitted medications: 1. With potential pro-cognitive effects, such as cholinesterase inhibitors, memantine, estrogen replacement therapy, must be at a stable dose for 1 month prior to screening and expected to remain stable throughout the study 2. Antidepressants must be at a stable dose for 1 month prior to screening and expected to remain stable throughout the study. 3. Antipsychotics must be must be at a stable dose for 1 month prior to screening and expected to remain stable throughout the study. 8. Willing and able to undergo repeated MRI scans (3 Tesla) with no contraindications to MRI. 9. Participant and partner must both be willing to use an effective contraception for duration of the study and for 4 days after it. For women, effective contraception may be hormonal; for men, a condom.
Exclusion criteria
Subjects must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in hallucinations/delusions as assessed by the Enhanced Scale for Assessment of Positive Symptoms in Parkinson's Disease (eSAPS-PD) | Screening, Baseline, Week 3, Week 6, Week 13, Week 16 | The eSAPS-PD is used to track changes in hallucinations and other psychotic symptoms over time. It was adapted from the scale for the assessment of positive symptoms (SAPS), which is used to track positive symptoms in patients with schizophrenia. The eSAPS-PD is a 13-item questionnaire which specifically assesses the frequency or severity of the most common types of hallucinations or delusions found in PD, namely auditory hallucinations, voices conversing, somatic or tactile hallucinations, visual hallucinations, persecutory delusions, delusions of jealousy and delusions of reference. In addition, the enhanced version assesses minor psychotic phenomena such as illusions, passage hallucinations, and presence hallucinations. Each item is rated from 0-5, with 0 representing none and 5 representing severe and frequent symptoms, and the total score ranges from 0 to 65. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in hippocampal overactivity as measured by fMRI (functional Magnetic Resonance Imaging) | Week 6, Week 16 | The secondary efficacy evaluation is confirmation of target engagement demonstrated by reduction in hippocampal overactivity comparing the end of the active treatment period compared to the end of the placebo treatment condition as measured by task-based functional magnetic resonance imaging. |
Countries
United States
Contacts
CONTACTCaroline L Wagandt, BA
CONTACTArnold Bakker, PhD
STUDY_DIRECTORArnold Bakker, Ph.D.
Johns Hopkins University
Outcome results
None listed