Study of Adults With Low Growth Hormone Who Survived Childhood Cancer Where Treatment Caused Low Bone Density

Study Overview
=================
Brief Summary
-----------------
The purpose of this project is to evaluate the hypothesis that bisphosphonate treatment given to growth hormone deficient patients (regardless of current growth hormone replacement therapy status and without changing that status) significantly increases total body bone mineral density during an eighteen month period of treatment combined with calcium and Vitamin D when compared to calcium and Vitamin D treatment alone.

Detailed Description
-----------------
Adult patients with Dexa scan (bone scan) z-scores < -1.0 (meaning low bone density) in at least one site will be selected for randomization. All patients who qualify for randomization will undergo baseline bloodwork for serum bone specific alkaline phosphatase (BSAP) and n-terminal telopeptides of collagen (NTX) levels. Recent bloodwork obtained as part of their ongoing long-term Pediatric Oncology and/or Endocrine clinic follow-up evaluation will be reviewed to exclude any baseline correctable confounding causes of osteopenia (low bone density). All women of childbearing potential will have a pregnancy test. For those patients already on growth hormone replacement therapy, growth hormone will be administered as per standard of care, with standard dose ranges adjusted based upon IGF-1(Insulin like growth factor) monitoring. Those patients not currently receiving growth hormone replacement therapy will not be placed on therapy as a part of this study. Patients on and off growth hormone replacement therapy will be randomized in a block design to the two treatment arms to assure equal numbers in each treatment arm. The bisphosphonate to be utilized will be provided to the Arm II patients at no charge. All Arm II patients will receive the same bisphosphonate regimen, Risedronate 35 mg per oral once weekly for 18 months. All patients on arms I and II will also receive Vitamin D (400 IU p.o. daily) and calcium carbonate (500 mg p.o. twice daily) free of charge for eighteen months.

Official Title
-----------------
Treatment of Childhood Cancer Therapy-induced Osteopenia in Growth Hormone Deficient Adult Survivors: Does Bisphosphonate Treatment Improve Bone Mineral Density?

Conditions
-----------------
Osteopenia

Intervention / Treatment
-----------------
* Drug: bisphosphonate therapy (risedronate)
* Dietary Supplement: Vitamin D supplement
* Dietary Supplement: Calcium


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Growth hormone deficiency as a complication of treatment for pediatric malignancy Dexa (bone densitometry)with z-scores of < -1.0 in at least one site Exclusion Criteria: Dexa (bone densitometry)with z-scores < -1.0 in at least one site Subjects <18 years old Pregnant or lactating patients Any contraindication for or unwillingness to consider bisphosphonate treatment Inability or unwillingness to undergo bone density evaluation Other correctable causes of decreased bone mineral density

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Growth Hormone only<br>No bisphosphonate therapy given, participants will take Vitamin D 400 IU daily for 18 months, as well as calcium carbonate 500 mg twice a day for 18 months. | Dietary Supplement: Vitamin D supplement<br>* Vitamin D given to patients with growth hormone deficiency<br>* Other names: Over the counter Vitamin D 400 IU.;Dietary Supplement: Calcium<br>* calcium supplement given to patients with growth hormone deficiency<br>|
| Experimental: Growth Hormone & Bisphosphonate Therapy<br>Bisphosphonate Therapy-Risedronate 35 mg once a week for 18 months, Vitamin D 400 IU daily for 18 months and calcium carbonate 500 mg twice daily for 18 months | Drug: bisphosphonate therapy (risedronate)<br>* Bisphosphonate therapy given to patients with growth hormone deficiency<br>Dietary Supplement: Vitamin D supplement<br>* Vitamin D given to patients with growth hormone deficiency<br>* Other names: Over the counter Vitamin D 400 IU.;Dietary Supplement: Calcium<br>* calcium supplement given to patients with growth hormone deficiency<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Body Bone Mineral Density During an 18 Month Period | For those patients already on growth hormone replacement therapy, growth hormone will be administered as per standard of care, with standard dose ranges adjusted based upon IGF-1 monitoring. Those patients not currently receiving growth hormone replacement therapy will not be placed on therapy as a part of this study. Patients on and off growth hormone replacement therapy will be randomized in a block design to the two treatment arms to assure equal numbers in each treatment arm. The bisphosphonate to be utilized will be provided to the Arm II patients at no charge. All Arm II patients will receive the same bisphosphonate regimen, Risedronate 35 mg per oral once weekly for 18 months. All patients on arms I and II will also receive Vitamin D (400 IU p.o. daily) and calcium carbonate (500 mg p.o. twice daily) free of charge for eighteen months. | 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
osteopenia, growth hormone deficiency, pediatric malignancy