Parkinson DiseasePhase 4APOMORPHEENCT02940912
Effect of Continuous Apomorphine During the Night on Sleep Disorders in Insomniac Patients With Parkinson's Disease
A Phase 4 study testing Apomorphine in people with Parkinson Disease, run by Clinique Beau Soleil at 9 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 90 years
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Apomorphine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 9 sitesFrance
- Study dates
- 31 Jan 2017to 12 Apr 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
France9 sites
Chu Gabriel Montpied
Clermont-Ferrand, 63001
Hôpital de la TIMONE
Marseille, 13385
Clinique Beau Soleil
Montpellier, 34070
CHU de NANTES - HOPITAL NORD
Nantes, 44093
CHU de NIMES
Nîmes, 30029
Chu Ponchaillou
Rennes, 35033
Hôpital CIVIL
Strasbourg, 67091
Hôpital de HAUTEPIERRE
Strasbourg, 67200
Centre hospitalier JACQUES LACARIN
Vichy, 03200
About this study
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
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.
Read the 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.
- Conditions
- Parkinson Disease
- Being tested
- Apomorphine, Placebo
- Keywords
- Parkinson disease, Insomnia, Sleep disorders, Polysomnography, Apomorphine, Multiple sleep latency test, Parkinson Disease Sleep Scale 2 (PDSS-2)
- Medical subject headings
- Parkinson Disease, Sleep Initiation and Maintenance Disorders, Sleep Wake Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApomorphineDrug
Also called Apokinon
cross-over with start with Apokinon in the 1st phase- in the 2nd phase of continuous treatment with Physiologic Serum.
PlaceboDrug
Also called Physiologic Serum
cross-over with start with.Physiologic Serum in the 1st phase- in the 2nd phase of continuous treatment with Apokinon.
| Study group | Role | What they receive |
|---|---|---|
| Apomorphine (5 mg/ml) | Active comparator | 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. Receives: Drug: Apomorphine |
| Physiologic serum | Placebo comparator | Physiological serum (from 0.1 ml to maximum 1 ml/ hour), delivered with a pump (subcutaneous administration), during 22 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline PDSS2 score (Parkinson's Disease Sleep Scale) at the end of the sequence
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).
Measured: 53 days
Secondary outcomes (13)
Total sleep time period
Variable will be measured from the polysomnography recordings
Measured: 53 days
Total sleep time (non-Rapid Eye Movements (REM) stages 1,2,3 plus REM sleep)
Variables will be measured from the polysomnography recordings
Measured: 53 days
Length of the intra-sleep wakefulness
Measured: 53 days
Sleep efficiency (total sleep time based on the total sleep period)
Measured: 53 days
Duration of each sleep stage of the total sleep time
Measured: 53 days
Subjective sleepiness on the Epworth Sleepiness Scale
Measured: 53 days
Sleep latency (between light extinction and the first period of sleep)
Measured: 53 days
Arousal index
Measured: 53 days
Apnea / hypopnea Index
Measured: 53 days
Percentage of time spent with a saturation below 90%
Measured: 53 days
Periodic leg movement index
Measured: 53 days
Percentage of REM sleep time with tonic and phasic activity
Measured: 53 days
Objective sleepiness on Multiple Sleep Latency Test
Measured: 53 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2016 (estimated)
- Study start31 Jan 2017
- Primary completion31 Jan 2021
- Study completion12 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinique Beau Soleil
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Valérie COCHEN DE COCK, PI, MD, PhD, Principal investigator, Clinique BEAU SOLEIL, 34070 MontpellierEmmanuel FLAMAND-ROZE, PI, MD, PhD, Principal investigator, Hopital PITIE-SALPETRIERE, 75013 Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02940912
- Sponsor's protocol ID
- 2015-005793-37
- Other IDs
- 2015
- Acronym
- APOMORPHEE
- Status last verified
- Feb 2021
- First submitted
- 14 Oct 2016
- Last updated
- 25 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 35429481
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02940912
- Acronym / sponsor ID
- APOMORPHEE / 2015-005793-37
- Conditions
- Parkinson Disease
- Keywords
- Parkinson disease, Insomnia, Sleep disorders, Polysomnography, Apomorphine, Multiple sleep latency test, Parkinson Disease Sleep Scale 2 (PDSS-2)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Clinique Beau SoleilUniversity, hospital or other
- Study start
- 31 Jan 2017 (actual)
- Primary completion
- 31 Jan 2021 (actual)
- Study completion
- 12 Apr 2021 (actual)
- First posted
- 21 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apomorphine (5 mg/ml) | Active comparator | Drug: ApomorphineActive 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. |
| Physiologic serum | Placebo comparator | Drug: PlaceboPhysiological serum (from 0.1 ml to maximum 1 ml/ hour), delivered with a pump (subcutaneous administration), during 22 days. |
Who may qualify
- Ages
- 35 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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) .
Key exclusion criteria (22 listed)
- Atypical Parkinsonian Syndromes
- Parkinson's disease with dementia (Montreal Cognitive Assessment (MoCA) <25/30 (NASREDDINE and al., 2012))
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApomorphineAlso: Apokinoncross-over with start with Apokinon in the 1st phase- in the 2nd phase of continuous treatment with Physiologic Serum. | Drug | Apomorphine (5 mg/ml) |
| PlaceboAlso: Physiologic Serumcross-over with start with.Physiologic Serum in the 1st phase- in the 2nd phase of continuous treatment with Apokinon. | Drug | Physiologic serum |
Primary outcome
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).
13 secondary outcomes
Total sleep time period
Time frame: 53 days
Total sleep time (non-Rapid Eye Movements (REM) stages 1,2,3 plus REM sleep)
Time frame: 53 days
Length of the intra-sleep wakefulness
Time frame: 53 days
Sleep efficiency (total sleep time based on the total sleep period)
Time frame: 53 days
Duration of each sleep stage of the total sleep time
Time frame: 53 days
Subjective sleepiness on the Epworth Sleepiness Scale
Time frame: 53 days
Sleep latency (between light extinction and the first period of sleep)
Time frame: 53 days
Arousal index
Time frame: 53 days
Apnea / hypopnea Index
Time frame: 53 days
Percentage of time spent with a saturation below 90%
Time frame: 53 days
Periodic leg movement index
Time frame: 53 days
Percentage of REM sleep time with tonic and phasic activity
Time frame: 53 days
Objective sleepiness on Multiple Sleep Latency Test
Time frame: 53 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- Derived from this study: PubMed 35429481De 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Valérie COCHEN DE COCK, PI, MD, PhD principal investigator
Clinique BEAU SOLEIL, 34070 Montpellier
Emmanuel FLAMAND-ROZE, PI, MD, PhD principal investigator
Hopital PITIE-SALPETRIERE, 75013 Paris
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Apomorphine in people with Parkinson Disease, run by Clinique Beau Soleil at 9 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline PDSS2 score (Parkinson's Disease Sleep Scale) at the end of the sequence (time frame: 53 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02940912, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2024; AzTrials last refreshed its copy on 6 Nov 2026.