Premature Newborns With Gestational Age 28 to 33 WeeksPREMODEURNCT02851979
Odors to Insufflate Life
A study testing Olfactory stimulations in people with Premature Newborns With Gestational Age 28 to 33 Weeks, run by Hospices Civils de Lyon at 2 sites in France.
Trial summary
Apneas concern about 85% of premature newborns (NB) born after less than 34 weeks of pregnancy. They are considered as an important risk factor for subsequent neuropsychological deficiency. Read more about this study
- Who is it for?
- Ages 6 days and older
- Conditions the study is for
- Premature Newborns With Gestational Age 28 to 33 Weeks
- What is being tested?
- Olfactory stimulations
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesFrance
- Study dates
- 9 Nov 2018to 28 Mar 2023
- Phase
- Interventional
- 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 6 days and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Newborns from a single or multiple pregnancy
- Newborns hospitalized in the Lyon East or Saint-Etienne neonatology services, of both sexes, born before 33 weeks of amenorrhea and after at least 6 days of life, without respiratory disease beside premature birth.
- Newborns must present at least 3 bradycardia during 3 days, or presenting apneas at observation.
- Newborns will be randomized if they present at least 3 apnea episodes per 24 hour monitored by RECAN for 3 consecutive days prior to randomization.
- Written informed consents obtained from the newborns parents or legal representatives
Who cannot join
- Severe congenital malformation
- History of allergic reaction to smell stimulation (cough, sneeze, watery eyes, breathing pauses)
- No social insurance
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: PREMODEUR. "Odors to Insufflate Life". Implementation of a Controlled Olfactory Sensorial Method to Decrease Apneas in Premature Newborns. Proof of Concept Study. Latin-square Open Study With Blind Evaluation of Primary Outcome.
Apneas concern about 85% of premature newborns (NB) born after less than 34 weeks of pregnancy. They are considered as an important risk factor for subsequent neuropsychological deficiency. Current pharmacological treatments are not very effective, and have side effects (agitation, irritability, sleep disorders, tachycardia). Some studies suggest that in NBs with apneas resisting to drugs, a permanent odorisation with a drop of vanillin on the incubator's pillow might reduce the frequency of apneas. This latin square design study will test a controlled olfactory stimulation method, i.e. an olfactometer which controls the odor duration, intensity, and sequence using three different odors, to reduce apneic episodes measured using 24-registration of heart and respiratory rates.
- Being tested
- Olfactory stimulations
- Keywords
- premature newborns, apneas prevention, olfactory stimulation, latin square design
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olfactory stimulationsOther
Odors are disseminated using a portable fragrance device, a prototype developed by a research unit, CNRS UMR5292. The device is outside the incubator, the only part inside is a disposable Teflon tube. The odor flux stimulates distally the NBs' nostrils. Odoriferous compounds are placed in glass tubes. This allows the olfactometer to deliver three distinct odors (to avoid habituation) in a random scheme: spearmint odor, vanilla odor, and grapefruit odor (chemicals registered by Chemical Abstracts Service), while controlling for intensity (amount of compound), duration, and odor sequence. For the vehicle period, the glass tubes remain empty.
Stimulations occur every 5 minutes, for 5 seconds, they are mixed in medical gas to avoid infection. There are three 24-hour periods, and two 24-hour wash out periods, followed by a maximum of 3 days of surveillance.
| Study group | Role | What they receive |
|---|---|---|
| S0 - S1 - S2 | Experimental | S0 = no stimulation; washout; S1 = vehicle; washout; S2 = olfactory stimulation Receives: Other: Olfactory stimulations |
| S0 - S2 - S1 | Experimental | S0 = no stimulation; washout; S2 = olfactory stimulation; washout; S1 = vehicle Receives: Other: Olfactory stimulations |
| S1 - S0 - S2 | Experimental | S1 = vehicle; washout; S0 = no stimulation; washout; S2 = olfactory stimulation Receives: Other: Olfactory stimulations |
| S1 - S2 -S0 | Experimental | S1 = vehicle; washout; S2 = olfactory stimulation; washout; S0 = no stimulation Receives: Other: Olfactory stimulations |
| S2 - S0 - S1 | Experimental | S2 = olfactory stimulation; washout; S0 = no stimulation; washout; S1 = vehicle Receives: Other: Olfactory stimulations |
| S2 - S1 - S0 | Experimental | S2 = olfactory stimulation; washout; S1 = vehicle; washout S0 = no stimulation Receives: Other: Olfactory stimulations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of respiratory pauses between S1 and S2
variation of the number of apnea episodes per 24hours -registered on the continuous heart / respiratory monitoring device, defined as a total cessation of breathing superior to 20 seconds (single apnea) or ≤ 20 seconds with decreased heart rate <80 beats / min) - between olfactory stimulation (S2) and placebo stimulation (S1).
Measured: per 24hours
Secondary outcomes (3)
difference of the number of apnea episodes between S1 and S2
difference of the number of apnea episodes between S1 and S2 adjusted on the order of stimulations, gestational age, concomitant treatments likely to interfere with breathing and their dosage
Measured: per 24hours
difference of the number of apnea episodes between S0 and S2
difference in the number of apnea episodes between olfactory stimulation (S2) and no stimulation (S0)
Measured: per 24hours
adverse events
Measured: up to day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2016 (estimated)
- Study start9 Nov 2018
- Primary completion28 Mar 2023
- Study completion28 Mar 2023
Why it stopped: few inclusions - DSMB recommendation
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Premature Newborns With Gestational Age 28 to 33 WeeksStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- HELENE GAUTHIER MOULINIER, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02851979
- Sponsor's protocol ID
- 69HCL16_0078
- Acronym
- PREMODEUR
- Status last verified
- Feb 2024
- First submitted
- 28 Jul 2016
- Last updated
- 15 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gauthier-Moulinier H, Nguyen HKA, Fischer C, Maucort-Boulch D, Remontet L, Guyon A, Cividjan A, Thevenet M, Galletti S, Cornaton E, Duchamp-Viret P. Automated intermittent olfactory stimulation to reduce apnea in preterm infants: results of the PREMODEUR randomized clinical trial. Eur J Pediatr. 2026 Aug 11;185(9):654. doi: 10.1007/s00431-026-07318-2.
PubMed 42579164Duchamp-Viret P, Nguyen HK, Maucort-Boulch D, Remontet L, Guyon A, Franco P, Cividjian A, Thevenet M, Iwaz J, Galletti S, Kassai B, Cornaton E, Plaisant F, Claris O, Gauthier-Moulinier H. Protocol of controlled odorant stimulation for reducing apnoeic episodes in premature newborns: a randomised open-label Latin-square study with independent evaluation of the main endpoint (PREMODEUR). BMJ Open. 2021 Sep 13;11(9):e047141. doi: 10.1136/bmjopen-2020-047141.
PubMed 34518252
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PREMODEUR. "Odors to Insufflate Life". Implementation of a Controlled Olfactory Sensorial Method to Decrease Apneas in Premature Newborns. Proof of Concept Study. Latin-square Open Study With Blind Evaluation of Primary Outcome.
- ClinicalTrials.gov ID
- NCT02851979
- Acronym / sponsor ID
- PREMODEUR / 69HCL16_0078
- Keywords
- premature newborns, apneas prevention, olfactory stimulation, latin square design
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: few inclusions - DSMB recommendation
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 9 Nov 2018 (actual)
- Primary completion
- 28 Mar 2023 (actual)
- Study completion
- 28 Mar 2023 (actual)
- First posted
- 2 Aug 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.
Apneas concern about 85% of premature newborns (NB) born after less than 34 weeks of pregnancy. They are considered as an important risk factor for subsequent neuropsychological deficiency. Current pharmacological treatments are not very effective, and have side effects (agitation, irritability, sleep disorders, tachycardia). Some studies suggest that in NBs with apneas resisting to drugs, a permanent odorisation with a drop of vanillin on the incubator's pillow might reduce the frequency of apneas. This latin square design study will test a controlled olfactory stimulation method, i.e. an olfactometer which controls the odor duration, intensity, and sequence using three different odors, to reduce apneic episodes measured using 24-registration of heart and respiratory rates.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| S0 - S1 - S2 | Experimental | Other: Olfactory stimulationsS0 = no stimulation; washout; S1 = vehicle; washout; S2 = olfactory stimulation |
| S0 - S2 - S1 | Experimental | Other: Olfactory stimulationsS0 = no stimulation; washout; S2 = olfactory stimulation; washout; S1 = vehicle |
| S1 - S0 - S2 | Experimental | Other: Olfactory stimulationsS1 = vehicle; washout; S0 = no stimulation; washout; S2 = olfactory stimulation |
| S1 - S2 -S0 | Experimental | Other: Olfactory stimulationsS1 = vehicle; washout; S2 = olfactory stimulation; washout; S0 = no stimulation |
| S2 - S0 - S1 | Experimental | Other: Olfactory stimulationsS2 = olfactory stimulation; washout; S0 = no stimulation; washout; S1 = vehicle |
| S2 - S1 - S0 | Experimental | Other: Olfactory stimulationsS2 = olfactory stimulation; washout; S1 = vehicle; washout S0 = no stimulation |
Who may qualify
- Ages
- 6 days and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Newborns from a single or multiple pregnancy
- Newborns hospitalized in the Lyon East or Saint-Etienne neonatology services, of both sexes, born before 33 weeks of amenorrhea and after at least 6 days of life, without respiratory disease beside premature birth.
- Newborns must present at least 3 bradycardia during 3 days, or presenting apneas at observation.
- Newborns will be randomized if they present at least 3 apnea episodes per 24 hour monitored by RECAN for 3 consecutive days prior to randomization.
- Written informed consents obtained from the newborns parents or legal representatives
Key exclusion criteria (3 listed)
- Severe congenital malformation
- History of allergic reaction to smell stimulation (cough, sneeze, watery eyes, breathing pauses)
- No social insurance
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 |
|---|---|---|
| Olfactory stimulationsOdors are disseminated using a portable fragrance device, a prototype developed by a research unit, CNRS UMR5292. The device is outside the incubator, the only part inside is a disposable Teflon tube. The odor flux stimulates distally the NBs' nostrils. Odoriferous compounds are placed in glass tubes. This allows the olfactometer to deliver three distinct odors (to avoid habituation) in a random scheme: spearmint odor, vanilla odor, and grapefruit odor (chemicals registered by Chemical Abstracts Service), while controlling for intensity (amount of compound), duration, and odor sequence. For the vehicle period, the glass tubes remain empty. Stimulations occur every 5 minutes, for 5 seconds, they are mixed in medical gas to avoid infection. There are three 24-hour periods, and two 24-hour wash out periods, followed by a maximum of 3 days of surveillance. | Other | S0 - S1 - S2, S0 - S2 - S1, S1 - S0 - S2, S1 - S2 -S0, S2 - S0 - S1, S2 - S1 - S0 |
Primary outcome
Number of respiratory pauses between S1 and S2
Time frame: per 24hours
variation of the number of apnea episodes per 24hours -registered on the continuous heart / respiratory monitoring device, defined as a total cessation of breathing superior to 20 seconds (single apnea) or ≤ 20 seconds with decreased heart rate <80 beats / min) - between olfactory stimulation (S2) and placebo stimulation (S1).
3 secondary outcomes
difference of the number of apnea episodes between S1 and S2
Time frame: per 24hours
difference of the number of apnea episodes between S0 and S2
Time frame: per 24hours
adverse events
Time frame: up to day 8
Results and safety
The study was stopped early (reason given: few inclusions - DSMB recommendation). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2024.
- Derived from this study: PubMed 42579164Gauthier-Moulinier H, Nguyen HKA, Fischer C, Maucort-Boulch D, Remontet L, Guyon A, Cividjan A, Thevenet M, Galletti S, Cornaton E, Duchamp-Viret P. Automated intermittent olfactory stimulation to reduce apnea in preterm infants: results of the PREMODEUR randomized clinical trial. Eur J Pediatr. 2026 Aug 11;185(9):654. doi: 10.1007/s00431-026-07318-2.
- Derived from this study: PubMed 34518252Duchamp-Viret P, Nguyen HK, Maucort-Boulch D, Remontet L, Guyon A, Franco P, Cividjian A, Thevenet M, Iwaz J, Galletti S, Kassai B, Cornaton E, Plaisant F, Claris O, Gauthier-Moulinier H. Protocol of controlled odorant stimulation for reducing apnoeic episodes in premature newborns: a randomised open-label Latin-square study with independent evaluation of the main endpoint (PREMODEUR). BMJ Open. 2021 Sep 13;11(9):e047141. doi: 10.1136/bmjopen-2020-047141.
- Individual participant dataSharing planned: No
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.
HELENE GAUTHIER MOULINIER principal investigator
Hospices Civils de Lyon
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Olfactory stimulations in people with Premature Newborns With Gestational Age 28 to 33 Weeks, run by Hospices Civils de Lyon at 2 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 5 inclusion and 3 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: stopped early, as of the sponsor's last update on 15 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: few inclusions - DSMB recommendation). Results are not available in the source record.
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?
Number of respiratory pauses between S1 and S2 (time frame: per 24hours). 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 NCT02851979, which also lists 2 linked publications.
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 15 Feb 2024.