Prader Willi Syndrome
Conditions
Keywords
Prader Willi
Brief 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 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.
Interventions
DRUGoxytocin
Intranasal administration
Sponsors
University Hospital, Toulouse
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 5 Months
Healthy volunteers
No
Inclusion criteria
* Infants with PWS genetically confirmed * Aged less than 5 months
Exclusion criteria
* Infants presenting hepatic insufficiency * Infants presenting renal insufficiency * Infants with abnormal ECG
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurence of Adverse Event | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NOMAS Score | Before and after 7 days of treatment | NOMAS score evaluate sucking/swallowing abilitites of infants during feeding; endpoint is the % of infants who reached a NOMAS score \<= 10 (normal score) |
| Videofluoroscopy of Swallowing Score | before and after 7 days of treatment | Videofluoroscopy of swallowing score (VFSS score) |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| First Arm 4IU of oxytocin every other day
oxytocin: Intranasal administration | 6 |
| Second Arm 4 IU of oxytocin daily
oxytocin: Intranasal administration | 6 |
| Third Arm 4 IU of oxytocin twice daily
oxytocin: Intranasal administration | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | First Arm | Second Arm | Third Arm | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 6 | 5 / 6 | 4 / 6 |
| serious Total, serious adverse events | 1 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
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.
Time frame: up to day 8 (Visit 8)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| First Arm | Occurence of Adverse Event | 10 number of adverse events |
| Second Arm | Occurence of Adverse Event | 9 number of adverse events |
| Third Arm | Occurence of Adverse Event | 6 number of adverse events |
Secondary
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)
Time frame: Before and after 7 days of treatment
Secondary
Videofluoroscopy of Swallowing Score
Videofluoroscopy of swallowing score (VFSS score)
Time frame: before and after 7 days of treatment