APOMORPHEE: Effect of Continuous Apomorphine During the Night on Sleep Disorders in Insomniac Patients With Parkinson's Disease

Sponsor

Clinique Beau Soleil (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02940912

Collaborator

(none)

Enrollment

Locations

Arms

39.9

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Drug: Apomorphine Drug: Placebo	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 31, 2018

Actual Primary Completion Date :

Jan 31, 2021

Anticipated Study Completion Date :

May 30, 2021

Arms and Interventions

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.	Drug: Apomorphine cross-over with start with Apokinon in the 1st phase- in the 2nd phase of continuous treatment with Physiologic Serum. Other Names: Apokinon
Placebo Comparator: Physiologic serum Physiological serum (from 0.1 ml to maximum 1 ml/ hour), delivered with a pump (subcutaneous administration), during 22 days.	Drug: Placebo cross-over with start with.Physiologic Serum in the 1st phase- in the 2nd phase of continuous treatment with Apokinon. Other Names: Physiologic Serum

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.

Drug: Apomorphine

cross-over with start with Apokinon in the 1st phase- in the 2nd phase of continuous treatment with Physiologic Serum.

Other Names:

Apokinon

Placebo Comparator: Physiologic serum

Physiological serum (from 0.1 ml to maximum 1 ml/ hour), delivered with a pump (subcutaneous administration), during 22 days.

Drug: Placebo

cross-over with start with.Physiologic Serum in the 1st phase- in the 2nd phase of continuous treatment with Apokinon.

Other Names:

Physiologic Serum

Outcome Measures

Primary Outcome Measures

Change from baseline PDSS2 score (Parkinson's Disease Sleep Scale) at the end of the sequence [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).

Secondary Outcome Measures

Total sleep time period [53 days]
Variable will be measured from the polysomnography recordings
Total sleep time (non-Rapid Eye Movements (REM) stages 1,2,3 plus REM sleep) [53 days]
Variables will be measured from the polysomnography recordings
Length of the intra-sleep wakefulness [53 days]
Sleep efficiency (total sleep time based on the total sleep period) [53 days]
Duration of each sleep stage of the total sleep time [53 days]
Subjective sleepiness on the Epworth Sleepiness Scale [53 days]
Sleep latency (between light extinction and the first period of sleep) [53 days]
Arousal index [53 days]
Apnea / hypopnea Index [53 days]
Percentage of time spent with a saturation below 90% [53 days]
Periodic leg movement index [53 days]
Percentage of REM sleep time with tonic and phasic activity [53 days]
Objective sleepiness on Multiple Sleep Latency Test [53 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Chu Gabriel Montpied	Clermont-Ferrand	France	63001
2	Hôpital de la TIMONE	Marseille	France	13385
3	Clinique Beau Soleil	Montpellier	France	34070
4	CHU de NANTES - HOPITAL NORD	Nantes	France	44093
5	CHU de NIMES	Nîmes	France	30029
6	Chu Ponchaillou	Rennes	France	35033
7	Hôpital CIVIL	Strasbourg	France	67091
8	Hôpital de HAUTEPIERRE	Strasbourg	France	67200
9	Centre hospitalier JACQUES LACARIN	Vichy	France	03200

Sponsors and Collaborators

Clinique Beau Soleil

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