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

February 8, 2021 updated by: Clinique Beau Soleil

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

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.

Study Overview

Status

Active, not recruiting

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

Interventional

Enrollment (Actual)

45

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

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

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 31, 2018

Primary Completion (Actual)

January 31, 2021

Study Completion (Anticipated)

May 30, 2021

Study Registration Dates

First Submitted

October 14, 2016

First Submitted That Met QC Criteria

October 19, 2016

First Posted (Estimate)

October 21, 2016

Study Record Updates

Last Update Posted (Actual)

February 10, 2021

Last Update Submitted That Met QC Criteria

February 8, 2021

Last Verified

February 1, 2021

More Information

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.

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