Effects of PTH Replacement on Bone in Hypoparathyroidism

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00395538
• Date of registration: 02/11/2006
• Prospective Registration: No
• Primary sponsor: National Institute of Dental and Craniofacial Research (NIDCR)
• Public title: Effects of PTH Replacement on Bone in Hypoparathyroidism
• Scientific title: Effects of PTH Replacement on Bone in Hypoparathyroidism
• Date of first enrolment: October 30, 2006
• Target sample size: 46
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00395538
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Austria, Italy, United States

Contacts

• Name: Rachel I Gafni, M.D.
• Affiliation: National Institute of Dental and Craniofacial Research (NIDCR)

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

DiGeorge Syndrome

Hypoparathyroidism

Intervention(s)

Drug: PTH 1-34

Primary Outcome(s)

Change in Bone Biopsy Cancellous Bone Volume (Cn.BV/TV) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Intracortical Bone Formation Rate Per Unit of Bone Surface (Ic.BFR/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Intracortical Mineralizing Surface (Bone Surface Based) (Ic.MS/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Cancellous Bone Formation Rate Per Unit of Bone Surface (Cn.BFR/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Endocortical Mineralizing Surface (Bone Surface Based) (Ec.MS/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Total Number of Cortical Pores Per mm^2 (Ct.Po.N) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Cancellous Mineralizing Surface (Bone Surface Based)(Cn.MS/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Endocortical Bone Formation Rate Per Unit of Bone Surface (Ec.BFR/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Secondary Outcome(s)

Change in Endocortical Osteoid Surface / Bone Surface (Ec.OS/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Total Area of Cortical Porosity (Ct.Po.Ar) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Number of Participants With Nephrolithiasis/Nephrocalcinosis [Time Frame: Baseline, 12-Month Visit, 24-Month Visit, 36-Month Visit, 48-Month Visit, and 60-Month Visit]

Perceived Interference (PI) of the Fatigue Symptom Inventory (FSI) [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Primary Bone Biopsy Measures Adjusted for HPTH Dose [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Z-score of Total Hip Bone Mineralization Density (BMD) Assessed by DXA [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits]

Average Severity Score of the Fatigue Symptom Inventory (FSI) [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Change in Cortex 1 Spectral Calcium Width From the Back-Scattered Electron Imaging of Bone-Biopsies [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Trabecular Thickness (Tb.Th) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

SF36 Mental Health Domain [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Change in Cancellous Osteoid Surface / Bone Surface (Cn.OS/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Cancellous Osteoid Thickness (Cn.O.Th) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Cancellous Bone Mineral Apposition Rate (Cn.MAR) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Average Thickness of Inner and Outer Cortices (Ct.Th) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Cortex 1 Spectral Calcium High From the Back-Scattered Electron Imaging of Bone-Biopsies [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

24 Hour Urine NTX Telopeptide [Time Frame: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Change in Endocortical Osteoid Thickness (Ec.O.Th) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Cortex 1 Spectral Calcium Low From the Back-Scattered Electron Imaging of Bone-Biopsies [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Z-score of Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits]

Z-score of Whole Body Bone Mineralization Density (BMD) Assessed by DXA [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits]

Change in Intracortical Bone Mineral Apposition Rate (Ic.MAR) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Endocortical Eroded Surface / Bone Surface (Ec.ES/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Intracortical Eroded Surface / Bone Surface (Ic.ES/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Composite Severity Score of the Fatigue Symptom Inventory (FSI) [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Change in Endocortical Adjusted Apposition Rate (Ec.AjAR) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Intracortical Osteoid Thickness (Ic.O.Th) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Intracortical Osteoid Surface / Bone Surface (Ic.OS/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Cortex 1 Spectral Calcium Mean From the Back-Scattered Electron Imaging of Bone-Biopsies [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Sensitivity Analyses of Female Menopause Status in the Primary Bone Biopsy Efficacy Models [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Serum Phosphorus [Time Frame: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Change in Intracortical Adjusted Apposition Rate (Ic.AjAR) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Serum Alkaline Phosphatase [Time Frame: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Raw 1/3 Radius Bone Mineralization Density (BMD) Assessed by DXA. [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Change in Trabecular Number (Tb.N) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Trabecular Separation (Tb.Sp) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Z-score of AP Spine Bone Mineralization Density (BMD) Assessed by DXA [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits]

Raw Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Raw Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Raw Total Hip Bone Mineralization Density (BMD) Assessed by DXA [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Raw Whole Body Bone Mineralization Density (BMD) Assessed by DXA [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

SF36 Bodily Pain Domain [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

SF36 Physical Role Limitations Domain [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

SF36 Social Function Domain [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Total Distance Walked During a 6-minute Walk [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Z-score of Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits]

Raw AP Spine Bone Mineralization Density (BMD) Assessed by DXA [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Serum Calcium [Time Frame: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

SF36 Vitality Domain [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Change in Cancellous Adjusted Apposition Rate (Cn.AjAR) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Cancellous Eroded Surface / Bone Surface (Cn.ES/BS) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Cortex 1 Spectral Calcium Peak From the Back-Scattered Electron Imaging of Bone-Biopsies [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Change in Endocortical Bone Mineral Apposition Rate (Ec.MAR) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Serum Osteocalcin [Time Frame: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

SF36 Emotional Role Limitations Domain [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

SF36 General Health Domain [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

SF36 Physical Function Domain [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Total Area of Inner and Outer Cortices (Ct.Ar) [Time Frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies]

Z-score of 1/3 Radius Bone Mineralization Density (BMD) Assessed by DXA. [Time Frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)]

Secondary ID(s)

07-D-0016

070016

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 08/01/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00395538