Clinical trial NCT04394143: Effect of AD128 to Treat Obstructive Sleep Apnea
Official title: Effect of AD128 on Obstructive Sleep Apnea Severity: a Randomized, Placebo-controlled, Double-blind, Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Sleep Apnea, Obstructive
Keywords: obstructive sleep apnea
pharmacologic treatment
sleepiness
vigilance
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
Collaborators: name: Apnimed
First posted: 2020-05-19
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a randomized, placebo-controlled, double-blind crossover study
Primary purpose: TREATMENT

Brief summary: This study evaluates the combination of two drugs (AD128), to treat obstructive sleep apnea (OSA) severity. After a baseline evaluation and during 7 days, half of the participants will randomly receive this drug combination (AD128) and the other will receive a placebo, i.e. a drug without pharmaceutical effect. Neither the participants, nor the investigators will know in which arm participants are until the end of the study. After one week of trial, an evaluation will be perform and will be follow by one week without any treatment. During the third and last week of trial, there will be a crossover of the groups, i.e. the participants of the first group who took the two drugs (AD128) during the first week will take a placebo and those who took the placebo will take the drugs combination.


Eligibility criteria: Inclusion Criteria:

* Adults (\>18 years and ≤ 65 years)
* New or previous diagnosis of OSA with an AHI \> 15/h on a polygraphic or polysomnographic recording (Participants already treated with continuous positive airway pressure (CPAP) or mandibular advancement device can be included but a 7-days wash-out period is required before the beginning of the protocol and CPAP usage will not be possible during the whole protocol duration),
* Informed Consent as documented by signature (Appendix Informed Consent Form)

Exclusion Criteria:

* History of seizures,
* History of glaucoma,
* History of benign prostatic hyperplasia, organic miction disorder or urinary retention,
* Gastrointestinal disease (e.g. stenosis, occlusion, ulcerative colitis, toxic megacolon, hiatal hernia...)
* Cardiac arrhythmia,
* History of bipolar disorder,
* Use of respiratory stimulants or depressants,
* Use of Hypnotics,
* Use of Central nervous system stimulants,
* Use of Monoamine oxidase inhibitors (MAOIs) antidepressant,
* Major depressive disorder,
* Central sleep apnea representing more than 10% of all respiratory events
* Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,
* Pregnant or breast feeding female participants or participants who intend to become pregnant during the study (However, there is no contraindication to contraception),
* Other clinically significant concomitant disease states (renal failure, hepatic dysfunction, severe cardiovascular or respiratory disease, myasthenia gravis, cerebral sclerosis),
* Known or suspected non-compliance, drug or alcohol abuse,
* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
* Participation in another study with investigational drug within the 30 days preceding and during the present study
* Use or morphinic and derivatives which may influence sleep,
* Refusal to be informed in case of incidental findings.

Primary outcomes:
measure: Apnea-hypopnea index (AHI)
timeFrame: Day 7 and 21
Secondary outcomes:
measure: Oxygen desaturation index (ODI)
timeFrame: Day 7 and 21
measure: Oxygen desaturation index (ODI) in REM and NREM
timeFrame: Day 7 and 21
measure: Hypoxic load
timeFrame: Day 7 and 21
measure: Hypoxic load in REM and NREM
timeFrame: Day 7 and 21
measure: Arousal index
timeFrame: Day 7 and 21
measure: Arousal index in REM and NREM
timeFrame: Day 7 and 21
measure: Pulse wave amplitude (PWA) drops
timeFrame: Day 7 and 21
measure: Pulse wave amplitude (PWA) drops in REM and NREM
timeFrame: Day 7 and 21
measure: Apnea-hypopnea index (AHI) in REM and NREM
timeFrame: Day 7 and 21
measure: Percentage of REM sleep
timeFrame: Day 7 and 21
measure: Percentage of N1
timeFrame: Day 7 and 21
measure: Percentage of N2
timeFrame: Day 7 and 21
measure: Percentage of N3
timeFrame: Day 7 and 21
measure: Percentage of alpha wave
timeFrame: Day 7 and 21
measure: Percentage of beta wave
timeFrame: Day 7 and 21
measure: Percentage of gamma wave
timeFrame: Day 7 and 21
measure: Percentage of theta wave
timeFrame: Day 7 and 21
measure: Percentage of delta wave
timeFrame: Day 7 and 21
measure: Reaction time PVT
timeFrame: Day 7 and 21
measure: Lapse PVT
timeFrame: Day 7 and 21
measure: Chronic Excessive daytime sleepiness (EDS)
timeFrame: Day 7 and 21
measure: Acute Excessive daytime sleepiness (EDS)
timeFrame: Day 7 and 21
measure: Sleep quality
timeFrame: Day 7 and 21
measure: Fatigue
timeFrame: Day 7 and 21
measure: Systolic and diastolic blood pressure
timeFrame: Day 7 and 21
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
Study officials:
affiliation: University Hospital of Lausanne (CHUV)
name: Raphael Heinzer, MD
role: PRINCIPAL_INVESTIGATOR
References: