Effects of PTH Replacement on Bone in Hypoparathyroidism
Condition: Hypoparathyroidism; DiGeorge Syndrome
MeSH terms: DiGeorge Syndrome; Hypoparathyroidism
Intervention: PTH 1-34
Intervention description: Given twice daily by subcutaneous
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Parathyroid; Bone Biopsy; Calcium-Sensing Receptor; Bone Density; Bone Turnover; Hypoparathyroidism

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 (Omega) 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 1 - 7 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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Age eligibility at screening:

                    1. Premenopausal 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 70 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.

        EXCLUSION CRITERIA:

          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 m(2), using
             the CKD-EPI equation(15).

          3. Allergy or intolerance to tetracycline antibiotics

          4. Pregnant or lactating or planning to become pregnant during the course of the study.
             (Women who are able to get pregnant must agree to use an effective form of birth
             control while in this study.).

          5. Perimenopausal 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 continuously at any time, prior to study
             entry

         16. Any cognitive impairment that limits the subject s ability to comply, independently or
             through the assistance of a legally authorized representative, with protocol
             procedures.

         17. Open epiphyses as determined by an X-ray of the hand and wrist in subjects < 21 years
             of age.