Effects of PTH Replacement on Bone in Hypoparathyroidism

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )
ClinicalTrials.gov Identifier:
NCT00395538
First received: November 2, 2006
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Hypoparathyroidism
DiGeorge Syndrome
Drug: Parathyroid Hormone 1-34
Drug: PTH 1-34
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of PTH Replacement on Bone in Hypoparathyroidism

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Iliac crest bone biopsy [ Time Frame: twice ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bone mineral density distribution [ Time Frame: twice ] [ Designated as safety issue: No ]
  • Biochemical changes [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]
  • DXA [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]
  • Renal US and CT [ Time Frame: Annually ] [ Designated as safety issue: Yes ]
  • CT Densitometry [ Time Frame: Annually ] [ Designated as safety issue: No ]
  • Questionnaires [ Time Frame: every six months ] [ Designated as safety issue: No ]
  • 6-minute walk test [ Time Frame: every 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 69
Study Start Date: October 2006
Estimated Study Completion Date: September 2022
Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Biopsy ramdomization
Subjects are randomized to have the second bone biopsy done 1,2, or 4 years after the start of PTH.
Drug: Parathyroid Hormone 1-34
N/A
Drug: PTH 1-34
Given twice daily by subcutaneous

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00395538

Contacts
Contact: Lori C Guthrie, R.N. (301) 594-0844 guthriel@mail.nih.gov
Contact: Rachel I Gafni, M.D. (301) 594-9924 gafnir@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Rachel I Gafni, M.D. National Institute of Dental and Craniofacial Research (NIDCR)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )
ClinicalTrials.gov Identifier: NCT00395538     History of Changes
Other Study ID Numbers: 070016, 07-D-0016
Study First Received: November 2, 2006
Last Updated: May 22, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Parathyroid
Bone Biopsy
Calcium-Sensing Receptor
Bone Density
Bone Turnover
Hypoparathyroidism

Additional relevant MeSH terms:
Hypoparathyroidism
DiGeorge Syndrome
22q11 Deletion Syndrome
Abnormalities, Multiple
Cardiovascular Abnormalities
Cardiovascular Diseases
Chromosome Disorders
Congenital Abnormalities
Craniofacial Abnormalities
Endocrine System Diseases
Genetic Diseases, Inborn
Heart Defects, Congenital
Heart Diseases
Lymphatic Abnormalities
Lymphatic Diseases
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Parathyroid Diseases

ClinicalTrials.gov processed this record on October 23, 2014