Clinical trial NCT02940912: Effect of Continuous Apomorphine During the Night on Sleep Disorders in Insomniac Patients With Parkinson's Disease
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson Disease
Keywords: Parkinson disease
Insomnia
Sleep disorders
Polysomnography
Apomorphine
Multiple sleep latency test
Parkinson Disease Sleep Scale 2 (PDSS-2)
Lead sponsor: Clinique Beau Soleil
Sponsor class: OTHER
First posted: 2016-10-21
Enrollment: 45
Sex: ALL
Minimum age (years): 35
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to demonstrate that continuous apomorphine treatment during the night compared with placebo improves sleep quality in insomniac patient with Parkinson's disease.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline PDSS2 score (Parkinson's Disease Sleep Scale) at the end of the sequence
timeFrame: 53 days
Secondary outcomes:
measure: Total sleep time period
timeFrame: 53 days
measure: Total sleep time (non-Rapid Eye Movements (REM) stages 1,2,3 plus REM sleep)
timeFrame: 53 days
measure: Length of the intra-sleep wakefulness
timeFrame: 53 days
measure: Sleep efficiency (total sleep time based on the total sleep period)
timeFrame: 53 days
measure: Duration of each sleep stage of the total sleep time
timeFrame: 53 days
measure: Subjective sleepiness on the Epworth Sleepiness Scale
timeFrame: 53 days
measure: Sleep latency (between light extinction and the first period of sleep)
timeFrame: 53 days
measure: Arousal index
timeFrame: 53 days
measure: Apnea / hypopnea Index
timeFrame: 53 days
measure: Percentage of time spent with a saturation below 90%
timeFrame: 53 days
measure: Periodic leg movement index
timeFrame: 53 days
measure: Percentage of REM sleep time with tonic and phasic activity
timeFrame: 53 days
measure: Objective sleepiness on Multiple Sleep Latency Test
timeFrame: 53 days
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Chu Gabriel Montpied
city: Marseille
country: France
facility: Hôpital de la TIMONE
city: Montpellier
country: France
facility: Clinique Beau Soleil
city: Nantes
country: France
facility: CHU de NANTES - HOPITAL NORD
city: Nîmes
country: France
facility: CHU de NIMES
city: Rennes
country: France
facility: Chu Ponchaillou
city: Strasbourg
country: France
facility: Hôpital CIVIL
city: Strasbourg
country: France
facility: Hôpital de HAUTEPIERRE
city: Vichy
country: France
facility: Centre hospitalier JACQUES LACARIN
Study officials:
affiliation: Clinique BEAU SOLEIL, 34070 Montpellier
name: Valérie COCHEN DE COCK, PI, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital PITIE-SALPETRIERE, 75013 Paris
name: Emmanuel FLAMAND-ROZE, PI, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: De Cock VC, Dodet P, Leu-Semenescu S, Aerts C, Castelnovo G, Abril B, Drapier S, Olivet H, Corbille AG, Leclair-Visonneau L, Sallansonnet-Froment M, Lebouteux M, Anheim M, Ruppert E, Vitello N, Eusebio A, Lambert I, Marques A, Fantini ML, Devos D, Monaca C, Benard-Serre N, Lacombe S, Vidailhet M, Arnulf I, Doulazmi M, Roze E. Safety and efficacy of subcutaneous night-time only apomorphine infusion to treat insomnia in patients with Parkinson's disease (APOMORPHEE): a multicentre, randomised, controlled, double-blind crossover study. Lancet Neurol. 2022 May;21(5):428-437. doi: 10.1016/S1474-4422(22)00085-0.