To investigate the effects of GH treatment on body composition, psychosocial development, psychomotor development, growth, glucose metabolism, serum lipids, cognition, behaviour, bone mineral density, quality of life and safety parameters in…
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
- Hypothalamus and pituitary gland disorders
- Mental impairment disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter will be the difference of the change in body fat
percentage between the treatment group and control group during the first six
months after the start of the study, as assessed by the DXA scan.
Secondary outcome
At baseline:
- Clinical characteristics of PWL
- (Epi)genetic abnormalities found in the subjects with PWL
- Baseline serum IGF-1 levels and GH peak levels during a GH stimulation test
(clonidine test).
A difference between the change during the first six months of the study in the
treatment versus the control group, in:
- Height, weight, head circumference
- Resting Energy Expenditure
- Lean body mass
- Laboratory parameters: glucose metabolism, serum lipids, thyroid hormone
levels, IGF-I and IGF binding proteins, ghrelin.
- Blood pressure
- Sleep-related breathing disorders.
- Cognition, behaviour and social emotional development
A difference between measurements at the start of the GH treatment and
measurements after twelve and 24 months in all subjects:
- Body fat percentage
- Height, weight, head circumference, sitting height, arm span, length of foot,
tibia and hand
- Resting Energy Expenditure
- Lean body mass
- Laboratory parameters: glucose metabolism, serum lipids, thyroid hormone
levels, IGF-I and IGF binding proteins, ghrelin.
- Blood pressure
- Sleep-related breathing disorders.
- Cognition, behaviour and social emotional development
Background summary
Knowledge on PWS and treatment options for children and young adults with PWS
has markedly improved over the last decade and are continuing to improve.
Currently, children start growth hormone (GH) therapy at a very young age and
receive multidisciplinary care by teams consisting of a physician, nurse,
psychologist, physiotherapist, dietician, speech therapists.
In the last decade there have been several reports about children and adults
with symptoms similar to patients with Prader-Willi Syndrome (PWS), but without
the Prader-Willi genotype. These patients have clinical characteristics of PWS,
without the typical genetic aberrations on chromosome 15 and are described as
Prader-Willi-like (PWL). The most well-known genetic defect associated with PWL
is (maternal) uniparental disomy of chromosome 14 (UPD14), but PWL has been
described in many patients with other genetic abnormalities. For children with
symptoms of PWS, without the typical genotype, treatment is not available. As a
result, these children with a rare and serious disorder do not receive the care
that could improve many aspects of their lives.
Study objective
To investigate the effects of GH treatment on body composition, psychosocial
development, psychomotor development, growth, glucose metabolism, serum lipids,
cognition, behaviour, bone mineral density, quality of life and safety
parameters in children with a PWS-like condition. To investigate the baseline
clinical characteristics and underlying (epi)genetic causes of children with a
Prader-Willi like phenotype and their relation with the effects and safety of
GH treatment.
Study design
This study will be a randomized, controlled GH trial for six months, followed
by an open label study for two years. In order to control for confounding
variables, all participants will be stratified according to gender, age, and
type of genetic defect. After stratification, participants will be randomly
allocated to either the group receiving GH treatment or to the control group
receiving standard care. After six months the participants in the control group
will also start the GH-treatment.
Intervention
GH treatment 1 mg/m2/day sc.
Study burden and risks
The participant risk and burden are low, particularly in view of the expected
benefit on body composition, metabolic health, cognition and quality of life.
Westzeedijk 106
Rotterdam 3016 AH
NL
Westzeedijk 106
Rotterdam 3016 AH
NL
Listed location countries
Age
Inclusion criteria
- Prader-Willi-like phenotype, according to the PWL criteria (see below), or
with a proven molecular diagnosis of a uniparental disomy of chromosome 14
(mUPD14), or a mutation or duplication in the 15q11.2-q13 region (PWS-critical
region).
- Absence of a molecular diagnosis of PWS. This includes a type 1 (from
breakpoint 1 to breakpoint 4) or type 2 (from breakpoint 2 to breakpoint 4)
deletion, a uniparental disomy or imprinting center defect of the 15q11.2-q13
region.
- Age:
o Boys: 4 to 16 years
o Girls: 4 to 14 years.
- Written informed consent. , PWL criteria:
The PWL phenotype is present in case of the following symptoms:
• Hyperphagia and/or rapid weight gain between the ages of 1 and 8 years
AND
• Developmental/psychomotor delay (IQ<85 and/or enrolment in a school for
children with special needs)
AND
• One or more of the following symptoms:
o Infantile central hypotonia
o Behavioural problems (temper tantrums, (auto)aggression, autistic and/or
obsessive compulsive behaviour
o Poor speech
o Vision abnormalities (e.g. myopia, esotropia)
o Short stature (as defined by < -2SD-score, or -2SD relative to the target
height)
o Small hands and feet for height and/or age.
N.B. Patients diagnosed with UPD14 or a mutation/duplication in the 15q11.2
(Prader-Willi critical) region do not have to meet the PWL-criteria.
Exclusion criteria
- Non-cooperative behavior
- Extremely low dietary intake of less than the minimally required intake
according to WHO
- Use of medication to reduce weight
- BMI > +4SD
- Height velocity <1 cm per year and/or closed epiphyseal growth plates, as
determined by an x-ray of the hand
- Pregnancy
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 | EUCTR2018-004729-97-NL |
| CCMO | NL68535.078.19 |