To Assess the Efficacy and Safety of Ceftriaxone in Patients With Mild to Moderate Parkinson's Disease Dementia
This is a randomized, double blinded, placebo-controlled Phase II study to investigate the efficacy and safety of ceftriaxone in patients with mild to moderate Parkinson's disease dementia (PDD).This study will enroll approximately 106 patients to have up to 84 evaluable subjects, and conduct in Chung Shan Medical University Hospital, National Taiwan University Hospital,Taichung Veterans General Hospital, Kaohsiung Medical University Hospital and Tungs' Taichung MetroHarbor Hospital.
Parkinson's disease (PD) is a common neurodegenerative disorder that can cause significant disability and decrease quality of life. It is a chronic and progressive disease which means the symptoms become worse over time.
Parkinson's disease dementia (PDD) is a decline in thinking and reasoning that develops in many people living with PD at least a year after diagnosis. An estimated 50 to 80 percent of patients with PD eventually experience dementia as the disease progresses. Key risk factors or correlation consistently associated with PDD are older age, more severe parkinsonism (particularly rigidity, postural instability and gait disturbance), male gender, certain psychiatric symptoms (depression, psychosis) and mild cognitive impairment. PDD has a unique clinical profile and neuropathology, commonly reported symptoms include changes in memory, concentration and judgment; trouble interpreting visual information; muffled speech; visual hallucinations; delusions, especially paranoid ideas; depression, irritability and anxiety; and sleep disturbances, including excessive daytime drowsiness and rapid eye movement sleep disorder.
The investigational product (IP) is 1 g of ceftriaxone powder manufactured by Sandoz Company reconstituted with 1% lidocaine as diluent before use. Ceftriaxone is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intramuscular or intravenous administration. Ceftriaxone is the drug substance of Rocephin first approved by FDA in 1984 as a cephalosporin antibiotic, and is clinically widely used and currently off patent.
The current main treatment goal of PDD focuses on the improvement of disease symptoms. However, the irreversible deterioration of cognitive and motor functions is the most challenge issue for therapeutic agent development. Ceftriaxone was found to have functions in reducing glutamatergic hyperactivity and excitotoxicity and may exhibit neuro-protective functions as the mechanism in PDD treatment. The therapeutic effects of ceftriaxone on the animal model of PDD showed ceftriaxone works on 1) preventing cognitive and motor deficits, 2) inhibiting dopaminergic degeneration and restoring neuronal density and activity in the striatum and SNc, 3) inhibiting cell loss and restoring neuronal density and activity in the hippocampus , 4) increasing neurogenesis in the substantia nigra and hippocampus dentate gyrus, 5) increasing glutamate transporter expression in the striatum and hippocampus , and 6) decreasing neuronal hyperactivity in the subthalamic nucleus (STN). The effects observed in the animal model of PDD have suggested ceftriaxone as a potential promising medical treatment for PDD patients to improve the cognitive and motor function defects. For such reasons, the investigators plan to conduct this phase II trial of ceftriaxone to determine the potential efficacy and obtain safety profiles in PDD patients.
Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 106 participants
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blinded, Placebo-controlled Phase II Study to Assess the Efficacy and Safety of Ceftriaxone in Patients With Mild to Moderate Parkinson's Disease Dementia
Actual Study Start Date: February 15, 2019
Estimated Primary Completion Date: July 31, 2020
Estimated Study Completion Date: December 31, 2020
- Experimental: Ceftriaxone
- Placebo Comparator: Placebo
|Date last updated at source||2019-02-19|
|Study start date||2019-02-15|
|Estimated primary completion date||2020-07-31|