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

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

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.

Study Overview

• Status: Unknown
• Conditions: Metabolic Diseases; Cancer
• Intervention / Treatment: Other: GH Replacement (NutropinAq®); Other: No additional treatment

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • The Leeds Teaching Hospitals Nhs Trust
    • Contact: R&I Administrator; Phone Number: 0113 392 0152; Email: leedsth-tr.lthtresearch@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 22 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients will be identified in the late effects endocrine clinic aged between 16-22 years, which are severely growth hormone deficient.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients to receive GH replacement; 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®); GH Replacement continued.
Patients who will not receive GH replacement; An additional 30 patients who elect not to receive growth hormone replacement will provide a parallel control data.	Other: No additional treatment; GH Replacement not continued.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: The Leeds Teaching Hospitals NHS Trust

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: February 9, 2015
• First Submitted That Met QC Criteria: December 14, 2015
• First Posted (Estimate): December 15, 2015

Study Record Updates

• Last Update Posted (Estimate): December 15, 2015
• Last Update Submitted That Met QC Criteria: December 14, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases
• Other Study ID Numbers: ED07/8440