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the Efficacy and Safety of Agomelatine in the Patients With Parkinson's Disease

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: NCT03977441
Recruitment Status : Not yet recruiting
First Posted : June 6, 2019
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
Chun-Feng Liu, Second Affiliated Hospital of Soochow University

Brief Summary:
Among the patients with Parkinson's disease, about 40%~50% will suffer from depression, 40% will suffer from anxiety, and 40%~60% will suffer from sleep disorder. These non-motor symptoms of Parkinson's disease will cause great physical and psychological pain and affect the quality of life seriously. Commonly used therapeutic drugs, such as selective serotonin reuptake inhibitor (SSRI) and clonazepam, can cause a variety of side effects, including serotonin syndrome, sexual dysfunction, daytime fatigue, insomnia, residual effects and increased risk of falls. Therefore, a new and more reasonable therapeutic choice should be sought. Agomelatine is a new type of antidepressant with novel mechanism, and can improve sleep structure and circadian rhythm. The aim of this multi-center randomized controlled trial (RCT) is to clarify the role of agomelatine in improving sleep disorders and depression in patients with Parkinson's disease

Condition or disease Intervention/treatment Phase
Parkinson Disease Depression Sleep Disorders Circadian Rhythm Disorders Drug: Agomelatine or PIacebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: treatment group: treated with agomelatine control group: treated with placebo
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: double-blind placebo control
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study: Evaluation of the Efficacy and Safety of Agomelatine in the Treatment of Sleep Disorders and Depression in Patients With Parkinson's Disease
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: control group
treated with Pramipexole 0.75mg/d(0.25mg tid)+placebo 25mg qn *2weeks than Pramipexole 0.75mg/d(0.25mg tid)+placebo 50mg qn * 10 weeks
Drug: Agomelatine or PIacebo
control group:Pramipexole+pIacebo experimental group:Pramipexole+Agomelatine
Other Name: Pramipexole

Experimental: experimental group
treated with Pramipexole 0.75mg/d(0.25mg tid)+Agomelatine25 mg qn *2weeks than Pramipexole 0.75mg/d(0.25mg tid)+Agomelatine 50mg qn * 10weeks
Drug: Agomelatine or PIacebo
control group:Pramipexole+pIacebo experimental group:Pramipexole+Agomelatine
Other Name: Pramipexole




Primary Outcome Measures :
  1. The efficacy of the treatment on the sleep disorders in Parkinson's disease evaluated by PSQI scale score change [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]
    The Pittsburgh sleep quality index (PSQI) is a widely used sleep evaluation scale in the Chinese population. The sensitivity and specificity of the PSQI (cut-off at 7) are 98.3% and 90.2%, respectively. PSQI has been used to evaluate the sleep disorders in patients with Parkinson's disease focusing on their sleep habits primarily.


Secondary Outcome Measures :
  1. The efficacy of the treatment on the sleep disorders in Parkinson's disease evaluated by PDSS, sleep diary and activity trackers [ Time Frame: PDSS:visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week); Sleep diary and activity trackers: 12 weeks, through study completion. ]

    The Parkinson disease sleep scale (PDSS) is used to analyze the underlying causes of sleep disorders based on the results of each factor. In 2010, the International Movement Disorder Society (MDS) recommended that both PDSS and PSQI can be used for the screening and assessment of sleep disorders in the Parkinson's disease.

    Sleep diary is an internationally recognized method to assist the examination of sleep disorders, and keeping recording a sleep diary every day is an effective therapy for some patients with insomnia.

    Activity trackers can monitor and track fitness-related metrics such as distance walked or run, calorie consumption, heartbeat and quality of sleep, which can be used as a reference of patients' sleep quality and circadian rhythm.


  2. The efficacy on the excessive daytime sleepiness of patients with Parkinson's disease [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]
    Scale: Epworth sleepiness scale(ESS) score change The Epworth Sleepiness Scale (ESS) is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most people engage in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'. The questionnaire takes no more than 2 or 3 minutes to answer.

  3. The efficacy on the fatigue of patients with Parkinson's disease [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]
    Scale:The Fatigue Severity Scale (FSS) score change The Fatigue Severity Scale (FSS) is a scale used in the evaluation of fatigue that affects patients. A list of statements/questions is provided. These statements are related to the different aspects of fatigue and how it affects the body. While rating the questions, one should make use of the scale with numbers from 1 to 7. If a person strongly agrees with a particular statement, the rating of 7 should be given. Strong disagreement is expressed by rating the question as 1. The sum total of ratings given to all questions is used to determine the degree or severity of fatigue that a person is suffering from. The total score of 36 or above calculated using the scale indicates that a person is suffering from fatigue-related health problem. A score that is lower than 36 shows that the health is normal.

  4. The efficacy on the circadian rhythm of patients with Parkinson's disease [ Time Frame: visit1(baseline),visit3(6th week),visit4(12th week) ]
    Scale: The Morningness-Eveningness Questionnaire (MEQ) score change Circadian rhythm disorder is a kind of important sleep disorder. Body temperature and hormone level changes are effective methods to determine the daily cycle, but these methods are cumbersome. The scale evaluation is much easier to implement. The Morningness-Eveningness Questionnaire (MEQ) is the most widely known questionnaire to assess circadian preference. Cut-off points were evaluated: a range of 14-52 for Evening types, 53-64 for neither types, and 65-86 for Morning types.

  5. The efficacy on the rapid eye movement sleep behavior disorder (RBD) of patients with Parkinson's disease [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]
    Scale: The Rapid Eye Movement Sleep Behavior Disorder Questionnaire-Hong Kong (RBDQ-HK) score change It has been reported that the incidence of RBD in nucleoproteins disease is 90% for multiple system atrophy (MSA) and 38-56% for Parkinson's disease (PD). Therefore, the proportion and severity of RBD in the Parkinson's disease were needed to screened through the RBD screening questionnaire. The rapid eye movement sleep behavior disorder questionnaire (RBDQ)-Hong Kong was the first tool developed for quantifying the severity of RBD. The RBDQ-HK is a self-administered questionnaire with 13 questions. The RBDQ-HK score can range from 0 to 100. The sum total of ratings given to all questions is used to determine the degree or severity of RBD that a person is suffering from. The higher the RBDQ-HK score is, the worse the symptoms are.The best cut-off score was 17/18.

  6. The efficacy on the depression of patients with Parkinson's disease [ Time Frame: visit1(baseline),visit3(6th week),visit4(12th week) ]
    Scales: The Hamilton Depression Scale-17 (HAMD-17) score change The Hamilton Depression Scale (HAMD) is a test measuring the severity of depressive symptoms in individuals, often those who have already been diagnosed as having a depressive disorder.In the 17-item version, nine of the items are scored on a five-point scale, ranging from 0 (not present) to 4 (severe). The remaining eight items are scored on a three-point scale, from 0 to 2, with zero representing absence of symptom, one indicating doubt that the symptom is present, and two representing clear presence of symptoms. Scores can range from 0 to 54. One formulation suggests that scores between 0 and 6 indicate a normal person with regard to depression, scores between 7 and 17 indicate mild depression, scores between 18 and 24 indicate moderate depression, and scores over 24 indicate severe depression.

  7. The efficacy on the anxiety of patients with Parkinson's disease [ Time Frame: visit1(baseline),visit3(6th week),visit4(12th week) ]

    Scales: The Hamilton Anxiety Scale(HAMA) score change

    The Hamilton Anxiety Scale(HAMA) is a widely used interview scale to measure the severity of a patient's anxiety, based on 14 parameters, including anxious mood, tension, fears, insomnia, somatic complaints and behavior at the interview. The major value of HAM-A is to document the results of pharmaco- or psychotherapy, rather than as a diagnostic or screening tool. It takes 15-20 minutes to complete the interview and scoring. Each item is simply given a 5-point score: 0 (not present) to 4 (severe). The HAMA score can range from 0 to 56. The best cut-off score was 14.


  8. The efficacy on the movement of patients with Parkinson's disease [ Time Frame: visit1(baseline),visit3(6th week),visit4(12th week) ]
    Scale: Unified Parkinson's Disease Rating Scale (UPDRS-III) score change The European Medicines Agency (EMA) guideline mentions the UPDRS II and III scales as accepted scales to measure the efficacy of a drug for Parkinson's Disease. The Unified Parkinson's Disease Rating Scale-III (UPDRS-III) is the most widely used scale currently available for the clinical evaluation of motor dysfunction in Parkinson's disease (PD). Each item is simply given a 5-point score: 0 (Absent) to 4 (Marked in amplitude and present most of the time). The UPDRS-III score can range from 0 to 56. The higher the UPDRS-III score is, the worse the symptoms are.

  9. The efficacy on the life quality of patients with Parkinson's disease [ Time Frame: visit1(baseline),visit3(6th week),visit4(12th week) ]
    Scale: Parkinson's Disease Questionnaire-8 (PDQ-8) score change Substantial evidence is available to suggest that the Parkinson's Disease Questionnaire (PDQ) is reliable, valid, responsive, acceptable and feasible as the tool for the assessment of quality of life in Parkinson's disease patients. For these reasons it has been widely adopted and generally considered the industry 'gold standard'. The PDQ is available in the 39-point PDQ-39 or the short form PDQ-8 (8 items). The PDQ-8 contains eight of the original 39 items of the PDQ-39; one item selected from each of the 8 scales.The PDQ-8 provides a reliable measure of overall health status and is ideal for studies in which a shorter questionnaire is preferred. Each item is simply given a 5-point score: 0 (Absent) to 4 (present most of the time). The PDQ-8 score can range from 0 to 32. The higher the PDQ-8 score is, the worse the symptoms are.

  10. Dosage and frequency of sedative and hypnotic drugs [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]
    Record the dosage and frequency of sedative and hypnotic drugs taken by the patients every visit and analyze the difference between two groups

  11. The Safety of Agomelatine in the Patients With Parkinson's Disease - the effect on the total number of red blood cells. [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]

    The total number of red blood cells will be monitored through the blood routine examination to see whether the number will change abnormally.

    Normal range of the total number of red blood cells is 4.0-5.50*10^12/L (male) and 3.5~5.0*10^12/L (female) (reference value range)


  12. The Safety of Agomelatine in the Patients With Parkinson's Disease - the effect on the total number of white blood cells. [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]

    The total number of white blood cells will be monitored through the blood routine examination to see whether the number will change abnormally.

    Normal range of the total number of white blood cells is 4-10*10^9/L (male) and 4-10*10^9/L (female) (reference value range)


  13. The Safety of Agomelatine in the Patients With Parkinson's Disease - the effect on the platelet count. [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]

    The platelet count will be monitored through the blood routine examination to see whether the number will change abnormally.

    Normal range of the platelet count is 100-300*10^9/L (male) and 100-300*10^9/L (female) (reference value range)


  14. The Safety of Agomelatine in the Patients With Parkinson's Disease - the effect on the concentration of the hemoglobin. [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]

    The concentration of the hemoglobin will be monitored through the blood routine examination to see whether it will change abnormally.

    Normal range of the concentration of the hemoglobin is 120-160*g/L (male) and 110-150*g/L (female) (reference value range)


  15. The Safety of Agomelatine in the Patients With Parkinson's Disease - the effect on the liver function [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]
    the liver function will be monitored through the examination of the alanine aminotransferase (ALT) and the aspartate aminotransferase (AST) in the biochemical routine examination Normal range of the concentration of the ALT is 0~40U/L (reference value range) Normal range of the concentration of the AST is 0~40U/L (reference value range)

  16. The Safety of Agomelatine in the Patients With Parkinson's Disease - the effect on the renal function [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]
    the renal function will be monitored through the examination of the creatinine (Cr) and the urea nitrogen (BUN) in the biochemical routine examination Normal range of the concentration of the Cr is 53~106umol/L (male) and 44~97umol/L (female) (reference value range) Normal range of the concentration of the BUN is 2.86-7.14mmol/L(reference value range)

  17. Adverse Event and Serious Adverse Event [ Time Frame: visit1(baseline),visit2(2ed week),visit3(6th week),visit4(12th week) ]
    Safety index



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • diagnosed as Parkinson's disease conforming to 2015 International Movement Disorder Society(MDS) diagnostic criteria
  • Hoehn-Yahr ≤ 3 at "open" stage
  • Mini-mental State Examination(MMSE) ≥ 24 points;
  • Pittsburgh Sleep Quality Index (PSQI) > 7 points;
  • HAMD-17 > 13 points
  • Pramipexole hydrochloride tablets 0.75mg / d (0.25mg tid) has been used stably for one month
  • Signed informed consent

Exclusion Criteria:

  • Parkinson's syndrome and Parkinsonism-Plus syndrome
  • Parkinson's movement symptoms are still fluctuating or the treatment of Parkinson's movement symptoms is unstable
  • Hepatitis B virus carriers/patients, hepatitis C virus carriers/patients, patients with impaired liver function or elevated transaminase levels above the upper limit
  • Other serious neurological diseases, mental illnesses and physical illnesses
  • History of alcohol and drugs dependence
  • Dementia
  • Combined treatment with CYP1A2 strong inhibitor (fluvoxamine, ciprofloxacin, rifampicin, amiodarone, mexiletine, atazanavir, etc.)
  • High suicide risk or suicide attempt within 6 months (third item of HAMD-17 ≥ 3)
  • Antidepressant medication or other psychiatric treatment in the past month
  • pregnant or lactating
  • intolerance or allergy to agomelatine active ingredients and excipients
  • other conditions that are not suitable for the study considered by the investigators

Information from the National Library of Medicine

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): NCT03977441


Contacts
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Contact: Chun-Feng Liu, MD +86 512 67783307 liucf@suda.edu.cn
Contact: Kang-Ping Xiong, MD +8613914050356 xikapi@163.com

Sponsors and Collaborators
Second Affiliated Hospital of Soochow University
Investigators
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Principal Investigator: Chun-Feng Liu, MD Second Affiliated Hospital of Soochow University
Publications of Results:
Other Publications:

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Responsible Party: Chun-Feng Liu, Professor, Second Affiliated Hospital of Soochow University
ClinicalTrials.gov Identifier: NCT03977441    
Other Study ID Numbers: JD-LK-2019-008-02
First Posted: June 6, 2019    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: There is a plan to make individual participant data (IPD) available to the other researchers, who participant in the study, since this is a muti-center study. The study protocol, statistical Analysis Plan (SAP), informed Consent Form (ICF), clinical Study Report (CSR) will be shared. And all the data collected by the single center will be reported back.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: The additional supporting information is shared during the whole period. The IPD will become available immediately after publication.
Access Criteria: Access of the IPD and any additional supporting information will be approved by the principal investigator

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Parkinson Disease
Sleep Wake Disorders
Parasomnias
Chronobiology Disorders
Disease
Depression
Pathologic Processes
Behavioral Symptoms
Mental Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Neurologic Manifestations
Pramipexole
S 20098
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Hypnotics and Sedatives
Central Nervous System Depressants