To Assess the Efficacy and Safety of Ceftriaxone in Patients With Mild to Moderate Parkinson's Disease Dementia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03413384|
Recruitment Status : Recruiting
First Posted : January 29, 2018
Last Update Posted : February 19, 2019
|Condition or disease||Intervention/treatment||Phase|
|Parkinson's Disease Dementia||Drug: Ceftriaxone Other: Placebo||Phase 2|
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)|
|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|
1 g ceftriaxone per day for Day 1, 3, and 5 per cycle on a 2 weekly cycle
Other Name: Ceftriaxone Sandoz powder for IV Injection
Placebo Comparator: Placebo
same amount volume of placebo will be given on Day 1, Day 3, and Day 5 per cycle on a 2 weekly cycle
Placebo per day for Day 1, 3, and 5 per cycle on a 2 weekly cycle
- Compare the treatment difference in mean net change in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score with time course [ Time Frame: from baseline to week 17 and 33 visits ]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).
- Changes in Unified Parkinson's Disease Rating Scale (UPDRS) score [ Time Frame: from baseline to week 17 and 33 visits ]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.
- Changes in Judgment of Line Orientation score [ Time Frame: from baseline to week 17 and 33 visits ]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.
- Changes in Mini-Mental State Examination (MMSE) score [ Time Frame: from baseline at week 17 and 33 visits ]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.
- Changes in Clinical Dementia Rating (CDR) Scale score [ Time Frame: from baseline to week 17 and 33 visits ]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.
- Changes in Color Trail Test score [ Time Frame: from baseline to week 17 and 33 visits ]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.
- Changes in MRI image for atrophy rate of brain [ Time Frame: from baseline to week 17 and 33 visits ]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.
- Changes in MRI image for dopaminergic projection from substantia nigra to striatum [ Time Frame: from baseline to week 17 and 33 visits ]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.
- Changes in Tc-99m TRODAT SPECT image [ Time Frame: from baseline to week 17 and 33 visits ]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.
- Net change of biomarker α-synuclein data [ Time Frame: from baseline to week 17 and 33 visits ]Patients' plasma samples will be collected to analyze α-synuclen by immunomagnetic reduction (IMR) assay kit developed by Magqu Company.
- Net change of biomarker Aβ42 data [ Time Frame: from baseline to week 17 and 33 visits ]Patients' plasma samples will be collected to analyze α-synuclen by immunomagnetic reduction (IMR) assay kit developed by Magqu Company.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03413384
|Contact: Jui-Chi Hsufirstname.lastname@example.org|
|Kaohsiung Medical University Hospital||Recruiting|
|Kaohsiung, Taiwan, 807|
|Contact: Ching-Kua Liu, M.D. +886-7-3121101 ext 6761 email@example.com|
|Principal Investigator: Ching-Kua Liu, M.D.|
|Chung Shan Medical University Hospital||Recruiting|
|Taichung, Taiwan, 402|
|Contact: An-Chih Chen, M.D. +886-4-24739595 ext 34834 firstname.lastname@example.org|
|Principal Investigator: An-Chih Chen, M.D.|
|Taichung Veterans General Hospital||Not yet recruiting|
|Taichung, Taiwan, 407|
|Contact: Ming-Hong Chang, M.D. +886-4-23741302 email@example.com|
|Principal Investigator: Ming-Hong Chang, M.D.|
|Tungs' Taichung MetroHarbor Hospital||Recruiting|
|Taichung, Taiwan, 435|
|Contact: Hung-Yi Hsu, M.D. +886-4-26581919 ext 4517 firstname.lastname@example.org|
|Principal Investigator: Hung-Yi Hsu, M.D.|
|National Taiwan University Hospital||Recruiting|
|Taipei, Taiwan, 100|
|Contact: Chun-Hwei Tai, M.D. +886-2-23123456 ext 65343 email@example.com|
|Principal Investigator: Chun-Hwei Tai, M.D.|