The aim of this project is to validate the hypothesis that intranasal insulin improves development and behaviour in children with Phelan-McDermid syndrome.
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary end point is developmental pace. Development is assessed by the
Bayley-III-NL (Dutch version of the Bayley-III, Bayley, 2006) or WPPSI-III-NL
(Dutch version of the WPPSI-III, Wechsler, 2009) dependent on the developmental
age of the children. Both the Bayley-III and the WPPSI are individually
administered tests that provide subtests and composite scores that represent
general functioning. Developmental pace is calculated as the difference in
developmental age equivalent between two assessments divided by the difference
in calendar age in months at the time of these assessments (typically 6
months), resulting in a value for developmental age increase / month.
Secondary outcome
The secondary end point is behaviour. Behaviour is assessed by the following
questionnaires: Vineland screener, ESSEON, CBCL1,5-5, and Brief-P. To evaluate
behaviour in several domains, raw scores are determined. Improvement of
behaviour is represented by the increase in test scores in a certain period
(typically 6 months).
Other study parameters are genotypic characteristics, phenotypic
characteristics and motor behaviour.
Background summary
Children with Phelan-McDermid syndrome have a severe general developmental
delay and behavioural problems. The syndrome is caused by a deletion of 22q13.3
and the neurological problems are thought to result from haploinsufficiency of
SHANK3. The SHANK3 protein is located in the postsynaptic density of neurons in
conjunction with the insulin receptor. Insulin exerts effects on signal
transduction and protein interactions in the postsynaptic density. It induces
rapid delivery of glutamate receptors to the cell surface and stimulates
expression of dendritic scaffolding protein PSD-95.
Previous studies with intranasally administered insulin show a beneficial
effect on cognitive function, declarative memory and behaviour. Moreover, a
pilot study with six children demonstrated that intranasal insulin improves
development and behaviour in children with the Phelan-McDermid syndrome. It is
hypothesized that a decreased availability of SHANK3 can be compensated by
insulin-mediated activation of PSD-95, explaining this supposed positive
effect.
Study objective
The aim of this project is to validate the hypothesis that intranasal insulin
improves development and behaviour in children with Phelan-McDermid syndrome.
Study design
Randomized double-blind placebo controlled stepped wedge design
Intervention
At the start of the clinical trial phase each patient is given a nose apray
which contains either insulin or placebo treatment. Groups with placebo will
change from placebo to intranasal insulin at different time points. From then
all patients remain under intranasal insulin until the end of the study.
Administration of the intranasal solution will occur 1 or 2 times per day, 1
puff in 1 or both nostrills, depending on body weight.
Study burden and risks
The burden and risks associated with participation are limited. For this study,
development of children will be assessed four times. Each assessment takes
maximal two hours. If children do not have sufficient attention span or if they
do not co-operate, testing will be ceased. Risks of severe adverse effects have
not been reported by previous studies. Adverse effects that have been reported
are mild and virtually always temporarily. Potential issues of concern are
transitory nasal irritation, rhinitis, spontaneous nosebleeds and headache.
Intranasal administration of insulin has been demonstrated to be safe and it
does not have systemic effects on blood glucose levels.
Oostersingel ingang 47
Groningen 9700 RB
NL
Oostersingel ingang 47
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
• Age between 12 months and 18 years 0 months old at 1-1-2013
• Proven SHANK3 deletion by array-comparative genomic hybridization (array-CGH)
• Parents need to speak and understand Dutch
Exclusion criteria
• A contra-indication for the use of intranasal application (e.g. anatomical obstruction)
• Severe perinatal brain damage (e.g. asphyxia, haemorrhage, infection)
• A metabolic or muscle disease responsible for neurological symptoms, independent of the 22q13 deletion
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-002873-77-NL |
| CCMO | NL41213.042.12 |