Transitional Growth Hormone (GH) Use in Growth Hormone Deficient (GHD) Cancer Survivors

Study Overview
=================
Brief Summary
-----------------
Cure rates for childhood malignancies have improved at a remarkable pace.With the increasing cure rate came recognition of the long-term detrimental effects of radiotherapy and chemotherapy, known as late-effects. Endocrine late-effects are particularly prevalent in childhood cancer survivors. Growth Hormone (GH) deficiency is common following radiation to the head and leads to impaired growth, hence GH replacement is given to achieve optimise final height in childhood. In the adult GH is important to maintenance of bone, muscle & fat mass; vascular risk factors; and quality of life. This observational study aims to determine the long-term effect of low dose GH replacement on development of bone, muscle and fat mass; vascular risk; and quality of life in the early years after achievement of final height, a time known as transition. GH is thought to be essential to development of bone, muscle, and fat mass during this time period. Patients will be identified in the late -effects endocrine clinic, aged 16-22yrs, who are severely GH deficient. 30 patients will be recruited to the study who wish to continue receiving GH replacement, all of whom will receive recombinant GH. An additional 30 patients who do not wish to receive GH replacement will provide a parallel control data. All patients will undergo baseline assessment including examination; routine blood tests; urine dipstick; measures on height, weight, waist, and 24 hour blood pressure. Measures will be repeated at six months, and then annually until 25 years of age. Bone density will be measured at baseline, after two years and at age 25yrs. Patients requesting GH replacement will require initial additional visits to teach self injection, then 2-4wkly to assess when correct dose of GH is achieved. The study will enable assessment of the beneficial effects of GH replacement during transition in GH deficient survivors of cancer to be realised.

Official Title
-----------------
A Phase IV, Single-Centre, Non-Randomised, Controlled, Open-Label Study to Assess the Use of Growth Hormone (GH) Replacement Therapy (NutropinAq®) During Transition in GH Deficient Survivors of Childhood Cancer to Optimise Somatic Growth & Well-Being

Conditions
-----------------
Metabolic Diseases, Cancer

Intervention / Treatment
-----------------
* Other: GH Replacement (NutropinAq®)
* Other: No additional treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 16--22 years inclusive. Both genders. Able to provide informed consent. Severe GH deficiency (peak GH<5mcg/l on stimulation). No GH replacement therapy during the three months preceding the baseline visit. Stable anterior pituitary hormone (i.e. sex steroids, hydrocortisone, thyroxine) therapy over the previous six months. Life expectancy >24 months. Exclusion Criteria: Acute critical illness (Patients suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma, acute respiratory failure, or similar conditions). Active malignant disease (i.e. undergoing active treatment or palliation). Patients treated for an intracranial malignancy should have completed therapy two years prior to entering the study. Active Cushing's disese or acromegaly Pregnancy or desire to conceive within the following year. Patients at risk of pregnancy will be screened by urine pregnancy (HCG) test at the baseline evaluation & treatment initiation visit. Breast feeding. Proliferative diabetic retinopathy. Sensitivity to GH or its preservative

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 22 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients to receive GH replacement<br>30 patients will be recruited to the study who wishes to continue receiving growth hormone replacement, all of whom will receive NutorpinAq Recombinant growth hormone | Other: GH Replacement (NutropinAq®)<br>* GH Replacement continued.<br>|
| Patients who will not receive GH replacement<br>An additional 30 patients who elect not to receive growth hormone replacement will provide a parallel control data. | Other: No additional treatment<br>* GH Replacement not continued.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the change in quality of life (QoL) at twelve months with that at baseline for the two treatment groups. For the primary endpoint this will be determined using the GH -specific instrument, the Adult Growth |  | 12 monthly intervals until the age of 25yrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| compare the change in QoL at each assessment timepoint versus to Baseline for the two treatment groups | three generic selfrating questionnaires | 12 monthly intervals until the age of 25yrs | 
| Psychological General WellBeing Schedule (PGWBS) | Questionnaire completed at 12 months | 12 monthly intervals until the age of 25yrs | 
| Shortform 36 (SF36) questionnaire | Questionnaire completed at 12 months | 12 monthly intervals until the age of 25yrs | 
| EuroQoL 5D (EQ5D) questionnaire | AGHDA SF36 PGWBS EQ5D | 12 monthly intervals until the age of 25yrs | 
| compare the change in body composition between the two treatment groups at each assessment timepoint versus Baseline. | Weight Height Waist & hip circumference Skin thickness Bioimpedance Total body DXA scan | 12 monthly intervals until the age of 25yrs | 
| compare the change in cardiovascular risk factors between the two treatment groups at each assessment every 12 months versus Baseline. |  | 12 monthly intervals until the age of 25yrs | 
| compare the change in bone mineral content between the two treatment groups at each assessment every 12 months versus Baseline. |  | 12 monthly intervals until the age of 25yrs | 
| compare the change in bone turnover between the two treatment groups at each assessment timepoint versus Baseline. | Measurements of: DXA Scan Total bone mineral content Bone mineral density at hips and lumbar spine Serum Osteocalcin 24-hour urinary excretion of deoxypyridinoline cross-links | 12 monthly intervals until the age of 25yrs | 
| To assess the safety of GH treatment (IGF-I, Blood glucose, HbA1C, Blood pressure, Side effect questionnaire, Adverse events, Scheduled or unscheduled laboratory findings, Changes in concomitant medication) | IGF-I Blood glucose HbA1C Blood pressure Side effect questionnaire Adverse events Scheduled or unscheduled laboratory findings Changes in concomitant medication | 12 monthly intervals until the age of 25yrs |