|- candidate number||19258|
|- NTR Number||NTR4722|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||7-aug-2014|
|- Secondary IDs||METC NL39636.068.12|
|- Public Title||Metabolic effects of Growth Hormone |
|- Scientific Title||Prospective study on the metabolic and linear growth effects of rhGH treatment in children with Kabuki Syndrome.|
|- hypothesis||The hypothesis is that rhGH treatment in children with KS results within 6 weeks in a change of metabolism recognizable as an increase of total energy expenditure (TEE). This change in metabolism can be used as a predictor of growth response in the first year of treatment and indicates a better body composition.|
Secondary hypothesis is that hypermobility is present in all children with Kabuki Syndrome, mainly in the lower extremities, leading to, sometimes sever, (sub)luxations. Treatment with rhGH will lead to an increase in muscle strenth and improvement of composition of connective tissue, thus diminishing morbidity due to hypermobility in children with Kabuki Syndrome.
|- Healt Condition(s) or Problem(s) studied||Growth hormone, Obesity, Metabolic syndrome, Cardiovascular disease, Hypermobility syndrome, Small stature|
|- Inclusion criteria||•Children with mutation in the KMT2D gene (also known as MLL2) or the KDM6A gene.|
•Children who meet at least four out of five KS characteristics:
o Facial features: long palpebral fissures with eversion of outer third, arched eyebrows with sparse outer half, prominent and/or misshapen ears, and depressed nasal tip.
o Skeletal abnormalities.
o Intellectual disability (mild to moderate).
o Postnatal short stature.
o Abnormalities of dermal ridges.
•Age ≥ four years.
|- Exclusion criteria||•Children with a chronological or bone age greater than 8 years for girls and 10 years for boys, because of the influence of puberty.|
•Extremely low dietary intake (less than minimal required intake for age according to WHO criteria).
•Use of medication that might interfere with growth during GH therapy, such as corticosteroids and sex steroids.
•Previous or active malignancy
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||1-apr-2013|
|- planned closingdate||1-dec-2015|
|- Target number of participants||20|
|- Interventions||All subjects receive recombinant human (rh)GH in accordance with international guidelines for developmental syndromes.|
The subjects will be included in a prospective study. Total body water (TBW), TEE, basal metabolic rate (BMR) and physical activity level (PAL) measurements are performed over a 6-wk period. Markers of metabolic risk factors will be determined during routine blood controls. During routine physical examinations assessment of hypermobility will be examined and photo’s will be made for calculating body proportions.
|- Primary outcome||Objective 1:|
Is there an increase in TEE during 6 weeks of treatment with rhGH in children with Kabuki Syndrome?
What is the relation between the short-term (6 weeks) change in TEE as measured with the DLW technique and the long term change in height SDS during treatment with rhGH after one and two years?
What is the effect of rhGH treatment on metabolic risk parameters typical for the metabolic syndrome in adults?
What are the characteristics of hyermobility in the Dutch children and adults with Kabuki Syndrome:
-What is the prevalence of hypermobility
-Which limbs / joints are affected by hypermobility, with or without (sub)luxation’s
Are existing assessment tools for hypermobility (Beighton and Bulbena scores) usable in this population?
What are the characteristics of body proportions in children with Kabuki Syndrome:
-How are the body proportions in Kabuki syndrome children?
-Are the body proportions in Kabuki syndrome children differently compared to the normal population?
|- Secondary outcome||-To assess the long-term (at start, after one and two years of treatment) term safety of growth hormone therapy on metabolic risk parameters and body composition.|
-Does rhGH treatment lead to a diminished degree of hypermobility and, because of that, to less (sub)luxations?
-Does the body composition changes during rhGH treatment?
|- Timepoints||After one year treatment and after two years of treatment.|
|- Trial web site|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||MD. D.A. Schott|
|- CONTACT for SCIENTIFIC QUERIES||MD. D.A. Schott|
|- Sponsor/Initiator ||Maastricht University Medical Center (MUMC+)|
(Source(s) of Monetary or Material Support)
|- Brief summary|
|- Main changes (audit trail)|
|- RECORD||7-aug-2014 - 31-aug-2014|