Effects of PTH Replacement on Bone in Hypoparathyroidism
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on December 08, 2011 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypoparathyroidism
Intervention: Parathyroild Hormone 1-34 (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: National Institute of Dental and Craniofacial Research (NIDCR) Overall contact: Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov
Summary
Hypoparathyroidism is a rare condition associated with a low level of parathyroid hormone
(PTH) in the blood. Hypoparathyroidism can be genetic and show up in childhood, or it can
occur later in life. If it occurs later, it is usually due to damage or removal of the
parathyroid glands during neck surgery. PTH helps control the amount of calcium in blood,
kidneys, and bones. Low levels of calcium in the blood can cause a person to feel sick. It
can cause cramping or tingling in the hands, feet, or other parts of the body. A very low
blood calcium can cause fainting or seizures.
The standard treatment for hypoparathyroidism is a form of vitamin D (calcitriol) and
calcium supplements. Keeping normal blood levels of calcium can be difficult. Sometimes
there is too much calcium in the urine even if the calcium levels in the blood are low. High
calcium in the kidneys and urine can cause problems such as calcium deposits in the kidney
(nephrocalcinosis) or kidney stones. High levels of calcium in the kidney may keep the
kidney from functioning normally. Treatment with PTH will replace the hormone you are
missing. Your disease may be better controlled on PTH than on calcium and calcitriol.
Researchers at the NIH have conducted prior studies to establish synthetic human parathyroid
hormone 1-34 (HPTH) as a treatment for hypoparathyroidism. Other studies have shown that PTH
may improve calcium levels in blood and urine. The primary purpose of this research study is
to evaluate the effects of synthetic human parathyroid hormone 1-34 (HPTH) replacement
therapy on bone in adults and teenagers with hypoparathyroidism.
The study takes 5 years to complete and requires 12 inpatient visits to the National
Institutes of Health Clinical Center in Bethesda, MD. The first visit will help the study
team decide whether you are eligible. This visit will last 2 to 3 days. After taking calcium
and calcitriol for 3 - 6 months you will return to the NIH Clinical Center for the baseline
visit. The baseline visit is the visit that you will start your PTH; you will also undergo a
bone biopsy during the visit. The baseline visit may last 7 to 10 days. You will then take
PTH twice a day for 5 years. You will be asked to return to the NIH clinical center every 6
months for 10 follow-up visits. During one of the follow-up visits, you will have a second
bone biopsy taken from the other hip. That second biopsy will be done after 1 year, 2 years,
or 4 years of taking PTH; the researchers will assign the timing of the second biopsy
randomly. You will be asked to go to your local laboratory for blood and urine tests
between each follow up visit. At first the blood tests will occur at least once a week.
Later, you will need to go to your local laboratory for blood tests at least once a month
and urine tests once every 3 months. The local laboratory visits and follow-up visits at the
NIH Clinical Center will help the study team determine whether the HPTH treatment is
controlling your hypoparathyroidism.
Clinical Details
Official title: Effects of PTH Replacement on Bone in Hypoparathyroidism
Study design: Primary Purpose: Treatment
Primary outcome: Vitamin D vs PTH effects on bone.
Secondary outcome: Vitamin D vs PTH effects on calcium metabolism.
Detailed description:
Hypoparathyroidism due to inadequate production or secretion of parathyroid hormone (PTH) is
associated with hypocalcemia, hyperphosphatemia, suppressed bone turnover and, oftentimes,
increased bone mass. It may be due to a variety of genetic disorders, autoimmune conditions
and infiltrative diseases or as a result of parathyroid gland injury or removal during neck
surgery. Unlike other hormone deficiencies where individuals are treated with replacement
hormones, hypoparathyroid patients are typically treated with calcium and vitamin D
analogues; however, both the treatment and the underlying disease can lead to
hypercalciuria, nephrocalcinosis and decreased renal function.
Prior studies at the NIH have been important in establishing synthetic human parathyroid
hormone 1-34 (HPTH) as a beneficial treatment for hypoparathyroidism, possibly superior to
conventional therapy with calcium and calcitriol. These noninvasive studies suggest that,
although there is no significant effect of long-term treatment with HPTH on bone mass, HPTH
therapy leads to a chronic high bone turnover state. The primary goals of this study are to
(1) better understand the effects of hypoparathyroidism on the skeleton, and (2) evaluate
the skeletal effects of hormone replacement therapy with HPTH in hypoparathyroidism. To
accomplish these goals, we will treat hypoparathyroid individuals with synthetic human PTH
1-34 for up to 5 years, periodically assessing skeletal changes through biochemical markers
and iliac-crest bone biopsies, which will allow for ultrastructural, cellular, and molecular
analyses. This study presents a unique opportunity, through the study of subjects with
hypoparathyroidism and their treatment with HPTH, to assess the role of HPTH in human
skeletal biology.
Eligibility
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Both.
Criteria:
- INCLUSION CRITERIA:
1. Age eligibility at screening:
1. Premeopausal women: aged 18 to 45 years,
2. Postmenopausal women: aged greater than or equal to 53 years to 70 years
and 5 years since last menses. For women without a uterus, subjects must
have a clinical history of menopause for at least 5 years and an FSH
greater than 30 U/L.
3. Men: aged 18 to 50 years,
2. Physician-diagnosed hypoparathyroidism of at least 1-year duration, confirmed by
medical record review. The investigators will confirm the diagnosis during the
screening visit at which time the subject must have an intact PTH < 30 pg/mL.
3. Willing to provide informed consent
EXCLUSION CRITERIA:
Subjects meeting any of the following criteria will not be enrolled:
1. Moderate to severe hepatic disease defined as hepatic transaminases (ALT and AST) >
2 times the upper limit of normal
2. Severe renal insufficiency defined as a calculated GFR < 25 mL/min/1. 73 m2, using
the CKD-EPI equation15.
3. Allergy or intolerance to tetracycline antibiotics
4. Pregnant or lactating.
5. Peri-or post-menopausal as defined by no menses for 6 months to 5 years and an FSH >
20 U/L at the screening and/or baseline visits.
6. Chronic diseases that might affect mineral metabolism such as diabetes, celiac
disease, Crohn's disease, Cushing's syndrome, or adrenal insufficiency
7. Concurrent treatment with doses of thyroid hormone intended to suppress thyroid
stimulating hormone below the assay's detection limit or persistent thyroid cancer
8. History of a skeletal disease unrelated to hypoparathyroidism, such as osteoporosis
or low bone density (defined as a DXA Z-Score < - 2 in all subjects or T-score < -2
in subjects greater than or equal to 20 year old), osteosarcoma, Paget's disease,
alkaline phosphatase > 1. 5 times the upper limit of normal, or metastatic bone
disease
9. History of retinoblastoma or Li-Fraumeni syndrome
10. History of treatment with bisphosphonates, calcitonin, tamoxifen, selective-estrogen
receptor modulators, or directed skeletal irradiation
11. Use of oral or intravenous corticosteroids or estrogen replacement therapy for more
than 3 weeks within the last 6 months
12. Use of depot medroxyprogesterone for contraception within the past 12 months
13. Chronic inadequate biochemical control with conventional therapy and/or calcium
infusion dependent
14. Seizure disorder requiring antiepileptic medications
15. Treatment with PTH for more than 2 weeks prior to study entry
16. Any cognitive impairment that limits the subject's or the subject's legally
authorized representative's ability to understand the protocol, provide informed
consent, or to comply with the protocol procedures
17. Unwillingness or inability to comply with protocol procedures
18. Open epiphyses as determined by an X-ray of the hand and wrist in subjects < 21
years of age.
Locations and Contacts
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting
Additional Information
NIH Clinical Center Detailed Web Page
Related publications: Chan JC, Young RB, Alon U, Mamunes P. Hypercalcemia in children with disorders of calcium and phosphate metabolism during long-term treatment with 1,25-dihydroxyvitamin-D3. Pediatrics. 1983 Aug;72(2):225-33. No abstract available. Chan JC, Young RB, Hartenberg MA, Chinchilli VM. Calcium and phosphate metabolism in children with idiopathic hypoparathyroidism or pseudohypoparathyroidism: effects of 1,25-dihydroxyvitamin D3. J Pediatr. 1985 Mar;106(3):421-6. Christiansen C, Rodbro P, Christensen MS, Hartnack B, Transbol I. Deterioration of renal function during treatment of chronic renal failure with 1,25-dihydroxycholecalciferol. Lancet. 1978 Sep 30;2(8092 Pt 1):700-3.
Starting date: October 2006
Last updated: November 30, 2011
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