An observational study in Infant, Small for Gestational Age, sponsored by Merck KGaA, Darmstadt, Germany. Completed at 28 sites in Spain. Per ClinicalTrials.gov, last updated 2019-02-27.
Sponsored by Merck KGaA, Darmstadt, Germany · Observational
This non-interventional study for prospective follow up of a cohort of 220 subjects born small for gestational age (SGA) is planned for the purpose of finding out if normalisation of adult height is associated or not with metabolic alterations and if true, their magnitude and relevance as well as to detect warnings throughout the treatment period that may be useful for prevention or therapy. This study would help in answering the question if the SGA and growth hormone (GH) association results in insulin resistance and if affirmative, who develops it as well as its impact on other metabolic parameters that precedes type 2 diabetes.
The small for gestational age (SGA) concept includes babies born to term whose weight and/or height is lower than two standard deviations (SD) below the mean. Pathologically short stature is understood as a stature of 2.5 SD below the mean for their age and an expected adult height adjusted to the parental height of one SD below the mean. These SGA children with a pathological short stature after four years of age are unsuitable for GH treatment. In fact, there is no other efficient treatment for short stature and insufficient development of these children other than GH. In addition to short stature, the SGA syndrome also includes resistance to insulin with the consequent risk of developing type 2 diabetes and other interrelated metabolic alterations like dyslipidemia and hypertension; and the glucose-insulin-insulin growth factors (IGFs)-proteins transport axis regulate growth as well as foetal metabolism and development. Independent from the possible maternal environmental causes, those born with SGA have low levels of somatomedin C (IGF-I) and its transport protein [Insulin-like growth factor binding protein 3 (IGFBP-3)] as well as fasting hyperinsulinemia. The low levels of IGF-1 and IGFBP-3 persist in those that do not present a catch-up growth and the insulin resistance is secondary to the somatotrope axis. Treatment with GH increases IGF-I and IGFBP3 levels but also the plasmatic level of fasting insulin and the long term net result of this combination is unknown.
An analysis has shown, that although during the first 2 years of GH treatment, there are no signs of glucose intolerance even though there is less sensitivity to insulin, there could be a greater incidence of type 2 diabetes in deficient children that have been treated with GH for a longer period. Treatment with GH, of children born SGA that have not caught-up their growth at 4 years of age, in the majority of cases achieves a good initial growth speed increase in order to continue to grow within normal limits and end up with an adult height that falls within normal. This is achieved with an authorised daily dose of 0.035 mg/kg (1 mg/m2/day). However, the question regarding the possible metabolic consequences of GH treatment of those born SGA remains unanswered in both forms, to find out if GH treatment increases or reduces resistance to insulin and other associated metabolic parameters and therefore, the risk of developing type 2 diabetes. Continued monitoring to adult height of a cohort of subjects born with SGA and treated with GH is the most efficient, easy and comfortable tool for answering that question.
OBJECTIVES
Primary objective:
Secondary objectives:
To find predictive factors for the possible changes in insulin sensitivity and its complex associated obesity, hypertension and high triglycerides type dyslipidemia with low high density lipoprotein (HDL)-cholesterol. For this, a relation between these metabolic factors and auxological parameters is to be identified.
a. The following are considered independent or predictive variables:
This is an observational study of a single cohort, without the possibility of a control group because those born with SGA, who experience a catch-up growth and enter normal auxology within the first four years of life are not subjected to a paediatric follow-up similar to those that do not catch-up to normal auxology and are treated with GH. Therefore, the same auxological and metabolic test results are not available in standard care. The collection of said parameters requires an "ad hoc" intervention and the study would be experimental or interventional. The observation period of this study encompasses from the start of treatment with GH up to a year after finishing the treatment for any reason. The starting age as well as the time treatment is ended will vary per subject. However, most subjects finish treatment once adulthood is reached. In accordance with clinical studies, the average observation period will probably be about 10 years. After the basal data is made available, the collection of data afterwards will be carried out once a year per subject.
Merck KGaA, Darmstadt, Germany is the lead sponsor of 269 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Children with growth disorder (current height \<-2.5 SD and height adjusted to parental stature \<-1 SD) in children born SGA with a weight and/or length at birth below -2 SD, that has not experimented a growth catch-up (growth speed \<0 SD during the last year) at 4 years old or afterwards.
Exclusion Criteria:
Changes in the insulin sensitivity index measured using HOMA-IR (Homeostasis Model Assessment for Insulin Resistance)
Once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason
Time frame: up to 10 years
Auxological parameter - Growth speed
Growth speed will be measured using a wall stadiometer and quantified and assessed in cm/year. Measurement occurs once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason.
Time frame: up to 10 years
Auxological parameter - Height
Height will be measured using a wall stadiometer and quantified in standard deviations (SDS). Measurement occurs once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason.
Time frame: up to 10 years
Auxological parameter - Weight in kilogram
Measurement occurs once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason.
Time frame: up to 10 years
Auxological parameter - Plasma insulin growth factor (IGF-I), measured at the local laboratory
Plasma IGF-1 will be quantified in ng/ml. Measurement occurs once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason.
Time frame: up to 10 years
Auxological parameter - Plasma insulin growth factor (IGF-I), measured at the central laboratory
Plasma IGF-1 will be quantified in ng/ml. Measurement occurs once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason.
Time frame: up to 10 years
Metabolic parameter - Fasting plasma insulin measured at the local laboratory
Fasting plasma insulin will be quantified in μU/ml. Measurement occurs once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason.
Time frame: up to 10 years
Metabolic parameter - Fasting plasma glucose measured at the local laboratory
Fasting plasma insulin will be quantified in mmol/l. Measurement occurs once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason.
Time frame: up to 10 years
Metabolic parameter - Plasma triglycerides measured locally
Plasma triglycerides will be quantified in mg/dl. Measurement occurs once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason.
Time frame: up to 10 years
Metabolic parameter - High density lipoproteins (HDL) cholesterol measured locally
HDL-cholesterol will be quantified in mg/dl. Measurement occurs once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason.
Time frame: up to 10 years
Metabolic parameter - Glycosylated haemoglobin (HbA1c)
HbA1c will be quantified in % over total Hb. Measurement occurs once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason.
Time frame: up to 10 years
Metabolic parameter - Blood pressure (BP)
BP will be measured in mmHg. Measurement occurs once a year per subject from the start of treatment with GH up to a year after finishing the treatment for any reason.
Time frame: up to 10 years
This study is completed, as verified in Feb 2019. You cannot join it, but the record below documents what was studied.
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Merck KGaA, Darmstadt, Germany