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, Kaohsiung Chang Gung Memorial Hospital, China Medical University Hospital, Changhua Christian Hospital, and Taipei Veterans General 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. Ceftriaxone is a kind of antibiotics, which has been marketed in many countries. This is the first time for ceftraxone treatment on PDD patient. The primary objective of this Phase II study is to evaluate the improvement of cognitive function in PDD patients with ceftriaxone administration. This study will enroll approximately 106 patients, and conduct in multiple hospitals in Taiwan. Recruitment number of each site will be adjusted according to its enrollment status under the competitive enrollment model. Subjects will receive either ceftriaxone or placebo in a 1:1 ratio. One of the subjects' main caregiver should be involved to get the information of function of daily life and help to complete scale evaluation. The study lasts about 33 weeks, during which eligible patients will be given 1 g/day/dose of ceftriaxone or placebo via injection 3 doses every cycle (2 weekly cycle), for a total of 16 cycles. And the subjects can choose to get injection either in the clinical site or in their house.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
100
1 g ceftriaxone per day for Day 1, 3, and 5 per cycle on a 2 weekly cycle
Placebo per day for Day 1, 3, and 5 per cycle on a 2 weekly cycle
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, Kaohsiung, Taiwan
Chung Shan Medical University Hospital
Taichung, Taichung, Taiwan
China Medical University Hospital
Taichung, Taichung, Taiwan
National Taiwan University Hospital
Taipei, Taipei, Taiwan
Taipei Veterans General Hospital
Taipei, Taipei, Taiwan
Changhua Christian Hospital
Changhua, Taiwan
Compare the treatment difference in mean net change in ADAS-Cog score with time course
ADAS-Cog is a validated instrument to assess dementia covering memory, orientation, language, praxis and consisting of 11 items. The total possible scores range from 70 (severe impairment) to 0 (no impairment).
Time frame: from baseline to week 17 and 33 visits
Changes in Unified Parkinson's Disease Rating Scale (UPDRS) score
The UPDRS system is a composite scale intended for rating patients with PD. Scores are rated as 0-4 (0-1 for some Part IV), representing 0=normal and 1 or 4=maximal deficit, symptoms, or impairment.
Time frame: from baseline to week 17 and 33 visits
Changes in Judgment of Line Orientation score
The Judgment of Line Orientation (JLO) test is a widely used measure of visuospatial judgment. A score of 17 or less is considered a sign of severe deficit.
Time frame: from baseline to week 17 and 33 visits
Changes in Mini-Mental State Examination (MMSE) score
The MMSE is a brief, quantitative measure of cognitive status in adults. The instrument examines orientation, registration, attention, calculation, recall, visuo-spatial abilities and language. The maximum score is 30, with higher scores indicating better cognitive function.
Time frame: from baseline at week 17 and 33 visits
Changes in Clinical Dementia Rating (CDR) Scale score
The CDR Scale is a 5-point scale used to characterize 6 domains of cognitive and functional performance applicable to related dementias: memory, orientation, judgment \& problem solving, community affairs, home \& hobbies, and personal care. This score is useful for characterizing and tracking a patient's level of impairment/dementia with 0=normal, 0.5 =very mild dementia, 1=mild dementia, 2=moderate dementia, 3=severe dementia.
Time frame: from baseline to week 17 and 33 visits
Changes in Color Trail Test score
Color Trail Test provides quantitative and qualitative information by two trials. The length of time to complete each trial is recorded, along with qualitative features of performance indicative of brain dysfunction, such as near-misses, prompts, number sequence errors, and color sequence errors.
Time frame: from baseline to week 17 and 33 visits
Changes in MRI image for atrophy rate of brain
Multimodal MRI examinations will be performed on a 3T MRI scanner with a standard 8-channel head coil. Region of interest in the brain will be evaluated for functional changes including atrophy rate from baseline data.
Time frame: from baseline to week 17 and 33 visits
Changes in MRI image for dopaminergic projection from substantia nigra to striatum
Multimodal MRI examinations will be performed on a 3T MRI scanner with a standard 8-channel head coil. Region of interest in the brain will be evaluated for functional changes including dopaminergic projection from baseline data.
Time frame: from baseline to week 17 and 33 visits
Changes in Tc-99m TRODAT SPECT image
SPECT assessment will use Tc-99m, a radio tracer with high selectivity and specificity for the striatum dopamine transporter (DAT) density evaluation. DAT density change from baseline will be calculated from region of interest drawn in the striatum by independent readers.
Time frame: from baseline to week 17 and 33 visits
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