Prader Willi SyndromePhase 1/2OTBB2NCT02205034
Evaluation of Tolerance, Suckling and Food Intake After Repeated Nasals Administrations of Oxytocin in PWS Infants
A Phase 1/2 study testing oxytocin in people with Prader Willi Syndrome, run by University Hospital, Toulouse at 1 site in France.
Trial summary
The Prader-Willi syndrome (PWS) includes severe neonatal hypotonia with impaired suckling leading to failure to thrive in the most severe cases, subsequently followed by an early onset of morbid obesity with hyperphagia and deficit of satiety, combined with other endocrine dysfunction probably due to hypothalamic… Read more about this study
- Who is it for?
- Ages 1 month to 5 months
- Conditions the study is for
- Prader Willi Syndrome
- What is being tested?
- oxytocin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteFrance
- Study dates
- May 2013to Jul 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 month to 5 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants with PWS genetically confirmed
- Aged less than 5 months
Who cannot join
- Infants presenting hepatic insufficiency
- Infants presenting renal insufficiency
- Infants with abnormal ECG
Trial locations and contacts
1 site in 1 country.
France1 site
Centre de réfrence Prader-Willi, Hospital of infants
Toulouse, 31059
About this study
The Prader-Willi syndrome (PWS) includes severe neonatal hypotonia with impaired suckling leading to failure to thrive in the most severe cases, subsequently followed by an early onset of morbid obesity with hyperphagia and deficit of satiety, combined with other endocrine dysfunction probably due to hypothalamic dysfunction. The pathophysiological mechanism of the occurrence of the 2 main nutritional phases of PWS is unknown. Swaab reported a deficit in the oxytocin (OT)-producing neurons of the paraventricular nucleus in the brain of these patients. In addition of its well-known anorexigenic effect, OT is involved in establishing and maintaining social codes. Moreover in a PWS mouse model generated from a MAGEL2 KO gene a single OT injection at 5 hr of life prevent the early death observed in 50 % of the new born mice by recovering normal suckling. Interestingly this effect is no longer observed if OT injection takes place later. Our hypothesis is that early administration of OT in babies with PWS may improve suckling and possibly infant-mother interactions. In our recent study (manuscript in preparation), we have shown that a single intranasal administration of OT is well tolerated. This escalating dose study is designed to evaluate the tolerance of repeated intranasal administration of OT in 3 steps (4IU every other day, 4 IU daily, 4IU twice daily) in babies younger than 5 months with PWS.
Read the detailed description
Prader-Willi syndrome (PWS) is a rare, complex multisystem genetic disorder arising from the lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. The syndrome includes severe neonatal hypotonia with impaired suckling leading to failure to thrive in the most severe cases, subsequently followed by an early onset of morbid obesity with hyperphagia and deficit of satiety, combined with other endocrine dysfunction probably due to hypothalamic dysfunction. The pathophysiological mechanism of the occurrence of the 2 main nutritional phases of PWS is unknown. Swaab reported a deficit in the oxytocin (OT)-producing neurons of the paraventricular nucleus in the brain of these patients. In addition of its well-known anorexigenic effect, OT is involved in establishing and maintaining social codes. Moreover in a PWS mouse model generated from a MAGEL2 KO gene a single OT injection at 5 hr of life prevent the early death observed in 50 % of the new born mice by recovering normal suckling. Interestingly this effect is no longer observed if OT injection takes place later. Our hypothesis is that early administration of OT in babies with PWS may improve suckling and possibly infant-mother interactions. In our recent study (manuscript in preparation), we have shown that a single intranasal administration of OT is well tolerated. This escalating dose study is designed to evaluate the tolerance of repeated intranasal administration of OT in 3 steps (4IU every other day, 4 IU daily, 4IU twice daily) in babies younger than 5 months with PWS.
- Conditions
- Prader Willi Syndrome
- Being tested
- oxytocin
- Keywords
- Prader Willi
- Medical subject headings
- Prader-Willi Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oxytocinDrug
Also called Oxytocin (Syntocinon)
Intranasal administration
| Study group | Role | What they receive |
|---|---|---|
| first arm | Active comparator | 4IU of oxytocin every other day Receives: Drug: oxytocin |
| second arm | Active comparator | 4 IU of oxytocin daily Receives: Drug: oxytocin |
| third arm | Active comparator | 4 IU of oxytocin twice daily Receives: Drug: oxytocin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurence of Adverse Event
Occurrence of adverse event, description and quantification of their severity, imputability to repeated intranasal administration of OT (4IU every other day, 4 IU daily, 4IU twice daily) during the 7 days following the first administration.
Measured: up to day 8 (Visit 8)
Secondary outcomes (2)
NOMAS Score
NOMAS score evaluate sucking/swallowing abilitites of infants during feeding; endpoint is the % of infants who reached a NOMAS score <= 10 (normal score)
Measured: Before and after 7 days of treatment
Videofluoroscopy of Swallowing Score
Videofluoroscopy of swallowing score (VFSS score)
Measured: before and after 7 days of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2014 (estimated)
- Study startMay 2013
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Prader Willi SyndromeStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maïthé TAUBER, Principal investigator, Endocrinologie pédiatrique, Hospital of Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02205034
- Sponsor's protocol ID
- 12 391 02
- Other IDs
- 1239102
- Acronym
- OTBB2
- Status last verified
- Jan 2024
- First submitted
- 22 Jul 2014
- Last updated
- 21 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Tauber M, Boulanouar K, Diene G, Cabal-Berthoumieu S, Ehlinger V, Fichaux-Bourin P, Molinas C, Faye S, Valette M, Pourrinet J, Cessans C, Viaux-Sauvelon S, Bascoul C, Guedeney A, Delhanty P, Geenen V, Martens H, Muscatelli F, Cohen D, Consoli A, Payoux P, Arnaud C, Salles JP. The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader-Willi Syndrome. Pediatrics. 2017 Feb;139(2):e20162976. doi: 10.1542/peds.2016-2976.
PubMed 28100688Viaux-Savelon S, Rosenblum O, Guedeney A, Diene G, Cabal-Berthoumieu S, Fichaux-Bourin P, Molinas C, Faye S, Valette M, Bascoul C, Cohen D, Tauber M. Dyssynchrony and perinatal psychopathology impact of child disease on parents-child interactions, the paradigm of Prader Willi syndrom. J Physiol Paris. 2016 Nov;110(4 Pt B):427-433. doi: 10.1016/j.jphysparis.2017.08.001. Epub 2017 Sep 1.
PubMed 28823614Borie AM, Dromard Y, Guillon G, Olma A, Manning M, Muscatelli F, Desarmenien MG, Jeanneteau F. Correction of vasopressin deficit in the lateral septum ameliorates social deficits of mouse autism model. J Clin Invest. 2021 Jan 19;131(2):e144450. doi: 10.1172/JCI144450.
PubMed 33232306
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Tolerance, Suckling and Food Intake After Repeated Nasals Administrations of Oxytocin in PWS Infants
- ClinicalTrials.gov ID
- NCT02205034
- Acronym / sponsor ID
- OTBB2 / 12 391 02
- Conditions
- Prader Willi Syndrome
- Keywords
- Prader Willi
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- May 2013
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 31 Jul 2014 (estimated)
- Results
- Posted 4 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Prader-Willi syndrome (PWS) includes severe neonatal hypotonia with impaired suckling leading to failure to thrive in the most severe cases, subsequently followed by an early onset of morbid obesity with hyperphagia and deficit of satiety, combined with other endocrine dysfunction probably due to hypothalamic dysfunction. The pathophysiological mechanism of the occurrence of the 2 main nutritional phases of PWS is unknown. Swaab reported a deficit in the oxytocin (OT)-producing neurons of the paraventricular nucleus in the brain of these patients. In addition of its well-known anorexigenic effect, OT is involved in establishing and maintaining social codes. Moreover in a PWS mouse model generated from a MAGEL2 KO gene a single OT injection at 5 hr of life prevent the early death observed in 50 % of the new born mice by recovering normal suckling. Interestingly this effect is no longer observed if OT injection takes place later. Our hypothesis is that early administration of OT in babies with PWS may improve suckling and possibly infant-mother interactions. In our recent study (manuscript in preparation), we have shown that a single intranasal administration of OT is well tolerated. This escalating dose study is designed to evaluate the tolerance of repeated intranasal administration of OT in 3 steps (4IU every other day, 4 IU daily, 4IU twice daily) in babies younger than 5 months with PWS.
Detailed description
Prader-Willi syndrome (PWS) is a rare, complex multisystem genetic disorder arising from the lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. The syndrome includes severe neonatal hypotonia with impaired suckling leading to failure to thrive in the most severe cases, subsequently followed by an early onset of morbid obesity with hyperphagia and deficit of satiety, combined with other endocrine dysfunction probably due to hypothalamic dysfunction. The pathophysiological mechanism of the occurrence of the 2 main nutritional phases of PWS is unknown. Swaab reported a deficit in the oxytocin (OT)-producing neurons of the paraventricular nucleus in the brain of these patients. In addition of its well-known anorexigenic effect, OT is involved in establishing and maintaining social codes. Moreover in a PWS mouse model generated from a MAGEL2 KO gene a single OT injection at 5 hr of life prevent the early death observed in 50 % of the new born mice by recovering normal suckling. Interestingly this effect is no longer observed if OT injection takes place later. Our hypothesis is that early administration of OT in babies with PWS may improve suckling and possibly infant-mother interactions. In our recent study (manuscript in preparation), we have shown that a single intranasal administration of OT is well tolerated. This escalating dose study is designed to evaluate the tolerance of repeated intranasal administration of OT in 3 steps (4IU every other day, 4 IU daily, 4IU twice daily) in babies younger than 5 months with PWS.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| first arm | Active comparator | Drug: oxytocin4IU of oxytocin every other day |
| second arm | Active comparator | Drug: oxytocin4 IU of oxytocin daily |
| third arm | Active comparator | Drug: oxytocin4 IU of oxytocin twice daily |
Who may qualify
- Ages
- 1 month to 5 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Infants with PWS genetically confirmed
- Aged less than 5 months
Key exclusion criteria (3 listed)
- Infants presenting hepatic insufficiency
- Infants presenting renal insufficiency
- Infants with abnormal ECG
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 |
|---|---|---|
| oxytocinAlso: Oxytocin (Syntocinon)Intranasal administration | Drug | first arm, second arm, third arm |
Primary outcome
Occurence of Adverse Event
Time frame: up to day 8 (Visit 8)
Occurrence of adverse event, description and quantification of their severity, imputability to repeated intranasal administration of OT (4IU every other day, 4 IU daily, 4IU twice daily) during the 7 days following the first administration.
2 secondary outcomes
NOMAS Score
Time frame: Before and after 7 days of treatment
Videofluoroscopy of Swallowing Score
Time frame: before and after 7 days of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28100688Tauber M, Boulanouar K, Diene G, Cabal-Berthoumieu S, Ehlinger V, Fichaux-Bourin P, Molinas C, Faye S, Valette M, Pourrinet J, Cessans C, Viaux-Sauvelon S, Bascoul C, Guedeney A, Delhanty P, Geenen V, Martens H, Muscatelli F, Cohen D, Consoli A, Payoux P, Arnaud C, Salles JP. The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader-Willi Syndrome. Pediatrics. 2017 Feb;139(2):e20162976. doi: 10.1542/peds.2016-2976.
- Results publication: PubMed 28823614Viaux-Savelon S, Rosenblum O, Guedeney A, Diene G, Cabal-Berthoumieu S, Fichaux-Bourin P, Molinas C, Faye S, Valette M, Bascoul C, Cohen D, Tauber M. Dyssynchrony and perinatal psychopathology impact of child disease on parents-child interactions, the paradigm of Prader Willi syndrom. J Physiol Paris. 2016 Nov;110(4 Pt B):427-433. doi: 10.1016/j.jphysparis.2017.08.001. Epub 2017 Sep 1.
- Derived from this study: PubMed 33232306Borie AM, Dromard Y, Guillon G, Olma A, Manning M, Muscatelli F, Desarmenien MG, Jeanneteau F. Correction of vasopressin deficit in the lateral septum ameliorates social deficits of mouse autism model. J Clin Invest. 2021 Jan 19;131(2):e144450. doi: 10.1172/JCI144450.
Related trials for Prader Willi Syndrome
RecruitingPhase 2
A Study of CSTI-500 in Patients With Prader-Willi Syndrome
Prader-Willi Syndrome
Recruiting
Cerebellar TMS and Satiety in Prader-Willi Syndrome
Prader-Willi Syndrome
Enrolling by invitationObservational study
Observational Study of VYKAT™ XR in Patients With Prader-Willi Syndrome
Prader-Willi Syndrome
Active, not recruitingPhase 1/2
A Study of RM-718 in Healthy Subjects and Patients With MC4R Pathway Impairment
Hypothalamic Obesity, Prader-Willi Syndrome
Active, not recruiting
Impact of Bright Light Therapy on Prader-Willi Syndrome
Prader-Willi Syndrome, Excessive Daytime Sleepiness
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.
Maïthé TAUBER principal investigator
Endocrinologie pédiatrique, Hospital of Toulouse
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing oxytocin in people with Prader Willi Syndrome, run by University Hospital, Toulouse at 1 site 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 2 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: finished, as of the sponsor's last update on 21 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 1 site 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Occurence of Adverse Event (time frame: up to day 8 (Visit 8)). 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 NCT02205034, which also lists 3 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 21 Feb 2024.