Growth Hormone and Chromosome 18q- and Abnormal Growth

Learn more about:
Related Clinical Trial
Assessment of Adherence, Quality of Life, Clinical Response and Safety of Daily and Long-Acting Growth Hormone Therapy Impact of GH Measurements on GHD Diagnosis Fluids Administration During Combined Clonidine-Arginine Growth Hormone Stimulation Test Three Month Treatment of Growth Hormone Releasing Hormone (GHRH) in the Elderly Free Fatty Acids, Body Weight, and Growth Hormones Secretion in Children A Single Dose Trial in Healthy Caucasians and Japanese Subjects Investigating the Pharmacokinetics of Somatropin Observational Study of Norditropin NordiFlex® With NordiFlex PenMate™ The Impact of the Use of Recombinant Human Growth Hormone on ADHD Characteristics in Children and Adolescents Constructing an Insulin-Like Growth Factor-based Prediction Model Peripheral Metabolic Effects of Somatostatin Chromosome 18 Clinical Research Center The Effect of Dietary Fat Load and Physical Exercise on the Flexibility and Partitioning of Ectopic Lipids. An Observational Study on Treatment Compliance by Children Treated With Growth Hormone A Single Dose Trial in Growth Hormone Deficient Children Investigating Safety, Pharmacokinetics and Pharmacodynamics of Long Acting Growth Hormone A Study to Compare the Uptake Into the Blood of Two Strengths of Somapacitan After Injection Under the Skin in Healthy Subjects Effectiveness of Growth Hormone Releasing Hormone in Reducing Abdominal Fat in People Who Are Obese Growth Hormone as Add-on Treatment in Severe Fibromyalgia With Low IGF-1 Serum Levels (56 Characters) A Study to Optimize Growth Hormone Dosing in Children With Chronic Kidney Disease by Measuring IGF-1 Levels in Blood Safety and Efficacy of Long-term Somatropin Treatment in Adults Dose Study in Growth Hormone Deficient Adults Investigating Safety, Pharmacokinetics and Pharmacodynamics of NNC126-0083 r-hGH Liquid Multidose Versus Freeze-dried Multidose Bioequivalence Trial Effects of Growth Hormone and IGF-1 on Anabolic Signals and Stem Cell Recruitment in Human Skeletal Muscle Genotropin Study Assessing Use of Injection Pen Treatment With Recombinant Human Growth Hormone Genotonorm (Registered) In Children With Short Stature Secondary Validation of a Questionnaire That Identifies the Reasons for Non-adherence to Existing Growth Hormone Therapy Treatment of Children With Insufficient Secretion of Growth Hormone Metabolic and QOL Effects of GH Treatment in Patients With TBI and AGHD Anterior Pituitary Hormone Replacement in Traumatic Brain Injury Evolution Of Growth Rate In Children With Growth Retardation Due to Glucocorticosteroid Therapy And Treated By Genotonorm Transition Study: Growth Hormone Therapy In Partial Growth Hormone Deficient Adolescents MOD-4023 (Long-Lasting Human Growth Hormone (hGH)) Study in Growth Hormone Deficient Adults (GHDA) Safety and Efficacy Phase 2 Study of Long-acting hGH (MOD-4023) in Growth Hormone Deficient Children Inter-Assay Growth Hormone and IGF-I Variability A Study to Evaluate Growth in Participants Treated With Somatropin (Nutropin) Using NuSpin Device Cardiovascular Risk in Growth Hormone Deficient Young Adult Males After Completing Growth Hormone Therapy Easypod United States User Trial National Cooperative Growth Study in CKD Low and Conventional Dose of Somatropin in Growth Hormone Deficient Adult Patients Practicability and Acceptability of Stylomax® in Children Growth Hormone’s Effect on the Cardiovascular System Exploring Interactions Between Growth Hormone and the Microbiome Pharmacokinetics and Pharmacodynamics of Long Acting Human Growth Hormone (hGH) Product (MOD-4023) in Healthy Caucasian and Japanese Volunteers A Phase 2, Safety and Dose-Finding Study in Treatment-Naive, Pre-Pubertal, Growth Hormone-Deficient Children Phase 1 Safety Study of ALRN-5281 in Healthy Subjects Safety, Pharmacokinetics and Pharmacodynamics Study of HL-032 in Healthy Male Volunteers Effect of Somatropin on Left Ventricular Mass in Growth Hormone Deficient Adult Patients Growth Hormone and Chromosome 18q- and Abnormal Growth An Observational Study Validating a Score That Quantifies the Therapeutic Response to Treatment With Norditropin® Cross Over Convenience And Preference Study Of New Mark VII Compared To Genotropin Pen In Pediatric And Adult Subjects A Multicentre, Randomised, Open-label, Controlled Study to Evaluate the Effects of Saizen® on Cardiac Function in Growth Hormone Deficient(GHD) Subjects During the Transition Phase From Childhood to Adulthood Study of TV-1106 in Growth Hormone-Deficient Adults Long Term Follow up Study of Long-acting hGH (MOD-4023) in Growth Hormone Deficient Children Long-Term Efficacy and Safety of Growth Hormone Replacement Therapy in Chronic Heart Failure Crossover Study to Assess the Safety and Pharmacokinetic of Pegylated Somatropin(PEG Somatropin) in GHD Children Study of an Extended-Release, Crystalline Formulation of Recombinant Human Growth Hormone (ALTU-238) in Growth Hormone Deficient Adults to Determine Pharmacokinetics, Pharmacodynamics, and Drug Safety Low Dose Growth Hormone (GH) on Insulin Sensitivity and Cortisol Production Rates Gene Expression in Monocytes of Growth Hormone Deficient Children Study of Pituitary Size and Function in Familial Dwarfism of Sindh Adipocyte Function and Somtropin Deficiency Sustained Release Formulation of Somatropin (rDNA Origin)for Injection Molecular Basis of the Growth Axis in Short Stature Cardiac and Skeletal Muscle Energy Metabolism in Abnormal Growth Hormone States The Effects of Growth Hormone (GH) on Lipid Depots The Effects of TZD on Fat Metabolism and Insulin Sensitivity in GH-Replaced GHD Patients Reference Values for Body Composition Parameters and IGF-I in the Adult NordiNet® International Outcome Study Effects of Growth Hormone Supplementation to Adults With Growth Hormone Deficient on Metabolism and Adipose Tissue Molecular Phenotype Sexually Dimorphic Effects of GHRH in Adult Growth Hormone Testing Metabolic Endocrinology and Growth Hormone in Adults Growth Hormone Treatment of Young Growth Hormone-Deficient Adults Safety and Efficacy of SR-hGH (Sustained-release Human Growth Hormone, Declage Inj.) rhGH Therapy on Hepatic Drug Metabolism Skeletal Muscle Effects of GH in Boys Assessment of Cardiovascular Risk Markers in Growth Hormone Deficient Patients With Nonsecreting Pituitary Adenomas Adipose Tissue and Serum Inflammation in GH Deficiency Adipose Tissue and Circulating Markers of Inflammation in GH Deficiency and Changes With GH Therapy

Brief Title

Growth Hormone and Chromosome 18q- and Abnormal Growth

Official Title

Growth Hormone Trial for Children With 18q- and Abnormal Growth

Brief Summary

      We, the investigators at the University of Texas Health Science Center at San Antonio, want
      to learn if height and IQ (intelligence quotient) scores are improved by growth hormone (GH)
      treatment in children with chromosome 18 deletions and abnormal growth. Data from a previous
      study showed that growth hormone improved height in all children with 18q- and growth hormone
      deficiency. In addition, most of the study participants on growth hormone treatment showed an
      increase in IQ scores.
    

Detailed Description

      HYPOTHESIS:

      Our hypothesis with reference to children with 18q deletions who have abnormal growth are:

        -  growth hormone will improve growth; and

        -  growth hormone will improve performance IQ (pIQ).

      Therefore, our specific aims are to evaluate the impact of GH treatment on:

        -  linear growth in children with 18q deletions who have abnormal growth but who are not
           classically growth hormone deficient; and

        -  pIQ in children with 18q deletions who have abnormal growth

      GOALS AND METHODS:

      We have already investigated the growth axis in 50 individuals with a cytogenetically and
      molecularly confirmed 18q deletion by determining the height, growth velocity, insulin-like
      growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), bone maturation and growth hormone
      (GH) response to pituitary stimulants (clonidine and arginine). To summarize: children with
      18q deletions are short: 64% have a height more than 2 S.D. below the mean. Affected children
      also grow slowly: 68% have a growth velocity more than 1 S.D. below the mean. Half of the
      individuals have delayed bone maturation. Growth factors are skewed downward: 72% of the IGF1
      values and 83% of the IGFBP3 values are below the average for normal children. Similarly, 72%
      of the children failed to adequately respond to the GH stimulants. In the total group of 50
      children, 20 (40%) were classically GH DEFICIENT (height <-2 S.D., velocity <-1 S.D., bone
      age <-2 S.D., IGF1 < -1 S.D., IGFBP3 <-1 S.D., peak GH <10 ng/ml by polyclonal GH assay) and
      are on GH treatment. Of the remaining 30 children, 28 have multiple abnormalities of the
      growth axis, primarily growth velocity <-1 S.D. (ABNORMAL GROWTH), but did not qualify for GH
      treatment according to criteria set by their private insurer. Almost all of these children
      had abnormalities suggestive of hypothalamic dysfunction involving TSH (thyroid stimulating
      hormone) and prolactin. None have CNS (central nervous system) abnormalities of the pituitary
      on MRI. Thus we suspect that many of these children have neurosecretory dysfunction. Parental
      heights are slightly above average (father (height standard deviation score) HTZ = 0.3 +/-
      1.2, mother HTZ = 0.1 +/- 1.1) and none of the children are overweight.

      Of 8 children with GHD (growth hormone deficiency) on prolonged GH treatment, growth rates
      are comparable to those reported by the NCGS (National Collaborative Growth Study) for
      idiopathic GHD at 1 and 2 years. The mean change in height over a 28-month period for the
      treated group in our study was +1.8 S.D. while it was -0.25 S.D. in the untreated group
      (p<0.001). No known complications of GH treatment were encountered. Furthermore, because of
      an association between 18q deletion, hypomyelination and cognition, some non-statural
      benefits of GH treatment were examined: specifically, the performance intelligence quotient
      (pIQ) was measured using a detailed battery of neuropsychological instruments. The pIQ was
      measured because many of the children are hearing impaired and a full scale IQ, which relies
      on verbal skills, would underestimate their abilities. The GH-treated group was compared to
      an untreated group. The GH-treated group (n=8) showed an increase in pIQ of 23 points (range
      0 to +47) while the untreated group (n=6) showed no change (range -2 to +6)(p=0.003). Based
      on these observations, we conclude that GHD children with 18q deletions respond favorably to
      GH therapy in terms of both linear growth and pIQ. In contrast, children with 18q deletions
      with abnormal growth who are not classically GH deficient, show little change in height S.D.
      and pIQ over time. Therefore, we propose to study (NEW STUDY) whether children with 18q
      deletions with abnormal growth can benefit from GH treatment. For purposes of this proposal,
      abnormal growth is defined as a growth velocity <-1 S.D.

      Initial auxology, endocrine testing, and neurocognitive evaluation will be performed at our
      Center. Auxologic and neurocognitive testing will be repeated after 18 months of therapy at
      our Center. These studies are done at our Center to assure consistency of evaluation, which
      is a particular concern for the neurocognitive tests. Many of the children will also
      participate in other studies in our Center (MRI imaging, psychological evaluations of family
      function) that are not part of this application. Children begun on GH treatment will need to
      be seen by a pediatric endocrinologist for dosage adjustment after 3, 6, 9 and 12 months. The
      untreated children will also need to be seen by a pediatric endocrinologist for auxologic
      studies at the same time points. We enrolled 20 children in this study. Few of the children
      are located in any single geographic area; therefore, we will have 12-20 centers seeing
      individual children. Rather than developing new forms, standard NCGS intake forms will be
      used for the intermediate visits by the local pediatric endocrinologists.

      Control Group: We have more than 20 previously studied children, 5.3 +/- 2.8 years of age,
      who have abnormal growth and have never received GH. All have undergone extensive auxologic,
      hormonal, neurocognitive and neuroimaging evaluations. These studies were done 15.4 +/- 9
      months ago (range 11-28 months). We have already shown that, in the absence of intervention,
      height S.D. and pIQ are stable over time; therefore, these children can serve as their own
      controls.

      We also have 20 children who are GH deficient and on treatment that are participants in
      another study. These children were evaluated prior to the initiation of treatment. All are
      scheduled to be re-evaluated at least twice in a five-year period. The data on the first 8
      treated children were reported above. These children will serve as important "disease
      controls".

      NAME OF FDA APPROVED DRUG TO BE USED:

      We are using Nutropin AQ in this study.

      METHOD OF TREATMENT ASSIGNMENT:

      All children who have previously been evaluated in our Center were offered the opportunity to
      receive GH, subject to the following limitations:

        -  The prior evaluation must have occured at least 12 months preceding the anticipated date
           of initiation of GH therapy.

        -  May not be on GH treatment or have been previously treated with GH

        -  Growth velocity <-1 S.D. with normal weight for length/height

        -  Must be willing to return to our Center for reevaluation of auxologic parameters and
           neurocognitive testing prior to the initiation of GH therapy.

        -  Must be willing to administer GH on a daily basis for 12-15 months

        -  Must be willing to return to our Center for re-evaluation after 12-15 months of therapy.

      The majority of the 20 patients for this study came from the group of children who have been
      previously evaluated.

      New children (families) being seen for their initial visit in our Center, will be offered the
      opportunity to participate in the clinical trial if they have abnormal growth and are not
      classically GHD. However, these children will be randomly assigned either to treatment or
      non-treatment for the initial 12-month period. Both treated and untreated children (families)
      must comply with limitations 2-6 above.

      The minority of the 20 patients for this study came from the group of children who are new.

      TYPE OF RANDOMIZATION:

      Randomization applied only to children who are new to our Center. When the results of growth
      factor and GH provocative testing are known, a two-step process will occur. Children, who are
      GHD, will be started on GH and entered into an on-going study already underway in our Center.
      They will not qualify for participation in the proposed NEW study. Children who have abnormal
      growth will be assigned to either the treatment or non-treatment category, using an adaptive
      randomization scheme to avoid imbalances in the numbers of subjects allocated to the two
      groups.

      PLANNED INTERIM ANALYSIS:

      GH-treated children will be seen at 3, 6, 9 and 12 months by their local pediatric
      endocrinologist for measurement of height and weight, review of medical history and dosage
      adjustment. Untreated children will be seen at 3, 6, 9, and 12 months for measurement of
      height and weight and review of medical history.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

growth rates 12-15 months after treatment begins

Secondary Outcome

 performance IQ scores 12-15 months after treatment begins

Condition

Loss of Chromosome 18q

Intervention

Nutropin AQ

Study Arms / Comparison Groups

 Growth Hormone Treatment
Description:  Arginine and Clonidine Stimulation Testing, Growth Factors Laboratory Testing, and Neuropsychological Testing was done 1st for eligibility and this group received GH (growth hormone) (Nutropin AQ) 0.3 mgs per kg per week (standard dosing for GH)immediately after randomization

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

20

Start Date

February 2001

Completion Date

June 2005

Primary Completion Date

June 2005

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of chromosome 18 deletion (cytogenetics report)

          -  Children with abnormal growth but who are not classically growth hormone deficient

        Exclusion Criteria:

          -  Children previously on growth hormone therapy
      

Gender

All

Ages

N/A - 18 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Daniel E. Hale, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00134420

Organization ID

300-C07


Responsible Party

Sponsor

Study Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

 South Texas Veterans Health Care System

Study Sponsor

Daniel E. Hale, M.D., Principal Investigator, The University of Texas Health Science Center at San Antonio


Verification Date

August 2016