- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02940912
Effect of Continuous Apomorphine During the Night on Sleep Disorders in Insomniac Patients With Parkinson's Disease (APOMORPHEE)
Double Bind Randomized Placebo-controlled Cross-over Study to Evaluate Effect of Continuous Apomorphine During the Night on Sleep Disorders in Insomniac Patients With Parkinson's Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Sleep disorders are very common in Parkinson's disease (PD). They are present in almost all patients. They have an important impact on quality of life. To improve the comfort of patients, neurologists typically offer either dispersible form of levodopa, prolonged release dopaminergic agonists treatments or deep brain stimulation surgery. Unfortunately these treatments are too short-acting for the dispersible form of levodopa or not always sufficient for the oral or transdermal dopamine agonist or are very heavy to implement as surgery.
Some sleep disorders such as restless legs syndrome and periodic leg movements, and obstructive sleep apnoea syndrome, seem to be more frequent in PD patients than in general population and could be improved by a continuous dopaminergic treatment the night.
Finally, daytime sleepiness is a major problem in PD patients. Although it seems most often linked to dopaminergic treatments given during the day, it could also be, in some patients the result of a very bad night's sleep, leading to a rebound of sleep during the day.
The main objective is to demonstrate that compared with placebo, nocturnal continuous apomorphine treatment improves sleep quality assessed by the patient on the PDSS-2 scale in fluctuating parkinsonian patients with complaints of insomnia.
The secondary objectives are to measure the effectiveness of nocturnal continuous apomorphine on sleep quality : total sleep time, sleep efficiency, arousal index, ventilatory events and legs movements indexes, to measure the relative proportion of sleep stages (N1, N2, N3, Rapid Eye Movement ou REM sleep), position changes during sleep index and the percentage of time spent in the supine position, percentage of time with SpO2 <90%), sleepiness (Epworth and Multiple Sleep Latency Test) and their consequences on quality of life (EuroQol 5), depressive symptoms (Beck II), anxiety (STAI), overall cognition (MOCA), pain and engine condition after waking up.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
Clermont-Ferrand, France, 63001
- CHU Gabriel Montpied
-
Marseille, France, 13385
- Hopital de La Timone
-
Montpellier, France, 34070
- Clinique Beau Soleil
-
Nantes, France, 44093
- CHU de NANTES - HOPITAL NORD
-
Nîmes, France, 30029
- CHU de Nîmes
-
Rennes, France, 35033
- CHU Ponchaillou
-
Strasbourg, France, 67200
- Hopital de Hautepierre
-
Strasbourg, France, 67091
- Hopital Civil
-
Vichy, France, 03200
- Centre Hospitalier Jacques Lacarin
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Idiopathic Parkinson's disease ( Hughes AJ et al. 2001)
- Patients with motor fluctuations
- Chronic Insomnia disorder criteria according to the criteria of DMS- V ( American Psychiatric Association, 2013) and insomnia severity index > 15
- Able to use independently the device required for treatment by apomorphine
- Collection of written informed consent (legal obligation for any project under the public health law , bioethics laws and / or CNIL) .
- Affiliate to social security or beneficiary of such a regime
Exclusion Criteria:
- Atypical Parkinsonian Syndromes
Parkinson's disease with dementia (Montreal Cognitive Assessment (MoCA) <25/30 (NASREDDINE and al., 2012))
- Parkinson's disease with hallucinations
- Parkinson's disease with impulse Control disorder (ICD)
- Parkinson's disease already treated with APOMORPHINE pump or justifying the use of the pump continuously day and night
- Another obvious severe disease explaining insomnia
- Exclusion for monitoring difficulties (mutation, insufficient motivation, priority associated pathology in care)
- Patient unwilling to accept a pump
- Patient not accepting polysomnography and multiple sleep latency test
- Patient with health problems or a skin disease precluding continuous subcutaneous infusion
- Female parturient or nursing
- Cardiac dysrhythmia precluding treatment with domperidone or apomorphine (increased QTc ≥ 440 ms in men, QTc ≥ 450 ms in women)
Treatments forbidden in association with apomorphine such as:
- antiemetic neuroleptics
- Tetrabenazine
- Excessive alcohol consumption
Contraindications for apomorphine:
- Hypersensitivity to apomorphine or one of the excipients
- Respiratory Depression
- Hepatic impairment
- Intellectual Disability
- Dementia
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Apomorphine (5 mg/ml)
Active phase is apomorphine (from 0.5 mg (0.1 ml) to maximum 5 mg (1 ml)/hour of apomorphine), delivered with a pump (subcutaneous administration), during 22 days.
|
cross-over with start with Apokinon in the 1st phase- in the 2nd phase of continuous treatment with Physiologic Serum.
Other Names:
|
Placebo Comparator: Physiologic serum
Physiological serum (from 0.1 ml to maximum 1 ml/ hour), delivered with a pump (subcutaneous administration), during 22 days.
|
cross-over with start with.Physiologic Serum in the 1st phase- in the 2nd phase of continuous treatment with Apokinon.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from baseline PDSS2 score (Parkinson's Disease Sleep Scale) at the end of the sequence
Time Frame: 53 days
|
This score is a score range, it's the difference between PDSS2 score at day18 and day 1 (for the first sequence) and difference between day 53 and day 36 (for the second sequence).
|
53 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total sleep time period
Time Frame: 53 days
|
Variable will be measured from the polysomnography recordings
|
53 days
|
Total sleep time (non-Rapid Eye Movements (REM) stages 1,2,3 plus REM sleep)
Time Frame: 53 days
|
Variables will be measured from the polysomnography recordings
|
53 days
|
Length of the intra-sleep wakefulness
Time Frame: 53 days
|
53 days
|
|
Sleep efficiency (total sleep time based on the total sleep period)
Time Frame: 53 days
|
53 days
|
|
Duration of each sleep stage of the total sleep time
Time Frame: 53 days
|
53 days
|
|
Subjective sleepiness on the Epworth Sleepiness Scale
Time Frame: 53 days
|
53 days
|
|
Sleep latency (between light extinction and the first period of sleep)
Time Frame: 53 days
|
53 days
|
|
Arousal index
Time Frame: 53 days
|
53 days
|
|
Apnea / hypopnea Index
Time Frame: 53 days
|
53 days
|
|
Percentage of time spent with a saturation below 90%
Time Frame: 53 days
|
53 days
|
|
Periodic leg movement index
Time Frame: 53 days
|
53 days
|
|
Percentage of REM sleep time with tonic and phasic activity
Time Frame: 53 days
|
53 days
|
|
Objective sleepiness on Multiple Sleep Latency Test
Time Frame: 53 days
|
53 days
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Valérie COCHEN DE COCK, PI, MD, PhD, Clinique BEAU SOLEIL, 34070 Montpellier
- Principal Investigator: Emmanuel FLAMAND-ROZE, PI, MD, PhD, Hopital PITIE-SALPETRIERE, 75013 Paris
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Parkinsonian Disorders
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Parkinson Disease
- Sleep Wake Disorders
- Parasomnias
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Gastrointestinal Agents
- Dopamine Agonists
- Dopamine Agents
- Emetics
- Apomorphine
Other Study ID Numbers
- 2015-005793-37
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Parkinson Disease
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedParkinson Disease 6, Early-Onset | Parkinson Disease (Autosomal Recessive, Early Onset) 7, Human | Parkinson Disease Autosomal Recessive, Early Onset | Parkinson Disease, Autosomal Recessive Early-Onset, Digenic, Pink1/Dj1United States
-
ProgenaBiomeRecruitingParkinson Disease | Parkinsons Disease With Dementia | Parkinson-Dementia Syndrome | Parkinson Disease 2 | Parkinson Disease 3 | Parkinson Disease 4United States
-
King's College LondonGlaxoSmithKlineCompletedParkinson Disease | Idiopathic Parkinson Disease | Parkinson Disease, PARK8United Kingdom
-
Ohio State UniversityCompletedParkinson's Disease | Parkinson Disease | Idiopathic Parkinson Disease | Idiopathic Parkinson's Disease | Parkinson Disease, Idiopathic | Parkinson's Disease, IdiopathicUnited States
-
National Yang Ming UniversityUnknownEarly Onset Parkinson Disease | Early Stage Parkinson Disease
-
Michele Tagliati, MDRecruitingREM Sleep Behavior Disorder | Symptomatic Parkinson Disease | Pre-motor Parkinson DiseaseUnited States
-
Cedars-Sinai Medical CenterEnrolling by invitationREM Sleep Behavior Disorder | Symptomatic Parkinson Disease | Pre-motor Parkinson DiseaseUnited States
-
Mahatma Gandhi Institute of Medical SciencesCompletedStroke, Parkinson' s Disease, Neurological Impairments, Tele-rehabilitationIndia
-
Merck Sharp & Dohme LLCCompletedParkinson Disease | Idiopathic Parkinson Disease | Idiopathic Parkinson's Disease
-
University of DeustoCompletedPARKINSON DISEASE (Disorder)Spain
Clinical Trials on Apomorphine
-
SunovionCompletedMotor OFF Episodes Associated With Parkinson's DiseaseSpain, United Kingdom, Germany, Italy, Austria, France
-
University Hospital, ToulouseCompletedParkinson's DiseaseFrance
-
University Hospital, RouenRecruitingPatients With Parkinson's Disease Treated With Apomorphine PumpsFrance
-
Oregon Health and Science UniversityNational Institute of Neurological Disorders and Stroke (NINDS)Withdrawn
-
Alexza Pharmaceuticals, Inc.ISS, Inc.; DSG; Peachtree BioResearch SolutionsTerminated
-
Mylan Bertek PharmaceuticalsCompleted
-
Mylan Bertek PharmaceuticalsCompletedParkinson DiseaseUnited States
-
Hospital Universitari Vall d'Hebron Research InstituteUnknown
-
Mylan Bertek PharmaceuticalsCompleted
-
Britannia Pharmaceuticals Ltd.CompletedParkinson's Disease