Clinical Trial Evaluating the Efficacy and Safety of AGB101 for Treatment of Parkinson's Disease Related Psychosis

Phase 2

Recruiting

• Conditions: Parkinson Disease Psychosis
• Interventions: Drug: AGB101

• Registration Number: NCT05824728
• Lead Sponsor: Johns Hopkins University

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.

Study Timeline

• Study First Submitted: 2023-04-06
• Study First Submitted QC: 2023-04-06
• Study First Posted: 2023-04-24
• Study Start: 2023-09-28
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-10
• Last Update Posted: 2024-10-14
• Primary Completion: 2026-09
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Subjects must not meet any of the following exclusion criteria at screening:

1. Use of anticonvulsant medications within 1 month prior to the baseline visit.
2. Participation in a therapeutic clinical study for any medical or psychiatric indications within 1 month of the screening visit, or at any time during the study. Subjects must understand that they may only enroll in this clinical study once; they may not enroll in any other clinical study while participating in the current study, and they may not participate in a clinical study of a drug, biologic, therapeutic device, or medical food, in which the last dose/administration was received within 1 month prior to screening.
3. History of hypersensitivity or lack of tolerability to AGB101 (levetiracetam).
4. Severe renal impairment (creatinine clearance of < 30 mL/minute) or undergoing hemodialysis.
5. Delirium due to the presence of an acute metabolic encephalopathy secondary to infection or from any other cause as assessed by the investigator based on labs, history, and physical exam.
6. Neurological disorder other than Parkinson's disease, such as Alzheimer's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder (lifetime history; infant febrile seizures are not exclusionary), subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits, or known structural brain abnormalities, that in the opinion of the investigator might interfere with the conduct of the study.
7. Prior diagnosis of schizophrenia, bipolar disorder or other psychotic disorder other than PD-related psychosis.
8. Stereotactic surgery for deep brain stimulation (DBS), presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body that constitute a contraindication to having an MRI scan.
9. History of alcohol or substance abuse or dependence within the past 3 years (DSM-5 criteria).
10. Any significant systemic illness or unstable medical condition that could lead to difficulty in complying with the protocol requirements.
11. Any unstable medical condition that is likely to require new medical or surgical treatment during the course of the study and where such treatments might affect the collection of efficacy data.
12. Unable or unwilling to provide informed consent or to comply with study procedures.
13. Patient or caregiver unable to administer daily oral dosing of study drug.
14. Current suicidal ideation.
15. Female subjects must not be pregnant or lactating.
16. Any other reason, which in the opinion of the investigator would confound proper interpretation of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
AGB101 first, then placebo	AGB101	AGB101 (low-dose levetiracetam, 220 mg, extended release tablet) once daily for 6 weeks, washout (4 weeks), then placebo capsule once daily for 6 weeks.
placebo first, then AGB101	AGB101	Placebo capsule once daily for 6 weeks, washout (4 weeks), then AGB101 (low-dose levetiracetam, 220 mg, extended release tablet) once daily for 6 weeks.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States