Effects of PTH Replacement on Bone in Hypoparathyroidism
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Change in Bone Biopsy Cancellous Bone Volume (Cn.BV/TV)
研究概览
简要总结
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.
详细描述
Objectives
The primary objective of this study is to evaluate the skeletal effects of hormone replacement therapy with HPTH in hypoparathyroidism.
Study Population
This study will enroll up to 69 subjects with physician-diagnosed hypoparathyroidism.<TAB>
Design
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Biopsy
Subjects are randomized to have the second bone biopsy done 1,2, or 4 years after the start of PTH.
干预措施: PTH 1-34 (Drug)
结局指标
主要结局
Change in Bone Biopsy Cancellous Bone Volume (Cn.BV/TV)
时间窗: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies
Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, so the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.BV/TV is one of 8 primary endpoints measured from the bone biopsy. The changes in Cn.BV/TV outcome between two time-points are being reported. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.
Change in Total Number of Cortical Pores Per mm^2 (Ct.Po.N)
时间窗: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies
Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, so the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ct.Po.N is a bone biopsy measure that assess the amount of holes in the cortical bone within a predetermined area of cortical bone. The changes in Cn.BV/TV outcome between two time-points are being reported. Cortical bone with a higher number of holes may be at greater risk of fracture. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).
Change in Endocortical Mineralizing Surface (Bone Surface Based) (Ec.MS/BS)
时间窗: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies
Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.MS/BS is measured from the bone biopsy. This measure demonstrates the percentage of the endocortical bone surface that is actively forming bone. The region of interest is the predefined area of total bone that is being measured. The changes in Ec.MS/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).
Change in Cancellous Bone Formation Rate Per Unit of Bone Surface (Cn.BFR/BS)
时间窗: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies
Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.BFR/BS, measured from the bone biopsy, is the cancellous bone formation rate per unit of bone surface where cancellous refers to the spongy structure of the bone. The changes in Cn.BFR/BS between two time-points are being reported. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.
Change in Cancellous Mineralizing Surface (Bone Surface Based)(Cn.MS/BS)
时间窗: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies
Following their baseline bone biopsy, 5, 5, and 2 participants were randomized to receive their second bone biopsy at years 1, 2, and 4 after the start of HPTH therapy, respectively. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced in size due to withdrawal and the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.MS/BS is measured from the bone biopsy. This measure demonstrates the percentage of the cancellous bone surface that is actively forming bone. The region of interest is the predefined area of total bone that is being measured. The changes in Cn.MS/BS between two time-points are being reported.
Change in Endocortical Bone Formation Rate Per Unit of Bone Surface (Ec.BFR/BS)
时间窗: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies
Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. However, because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.BFR/BS is measured from the bone biopsy. This measures the rate of new bone formation per day on the inner cortical (endocortical) surface in a predefined region of cortical bone. The changes in Ec.BFR/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).
Change in Intracortical Bone Formation Rate Per Unit of Bone Surface (Ic.BFR/BS)
时间窗: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies
Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. However, because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.BFR/BS is measured from the bone biopsy. This measures the rate of new bone formation between the two cortical surfaces (intracortical) in a predefined region of cortical bone. The changes in Ic.BFR/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).
Change in Intracortical Mineralizing Surface (Bone Surface Based) (Ic.MS/BS)
时间窗: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies
Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.MS/BS is measured from the bone biopsy. This measure demonstrates the percentage of the intracortical bone surface that is actively forming bone. The region of interest is the predefined area of total bone that is being measured. The changes in Ic.MS/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).
次要结局
- Change in Cancellous Osteoid Thickness (Cn.O.Th)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Cancellous Bone Mineral Apposition Rate (Cn.MAR)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Cancellous Osteoid Surface / Bone Surface (Cn.OS/BS)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Trabecular Thickness (Tb.Th)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Trabecular Separation (Tb.Sp)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Average Thickness of Inner and Outer Cortices (Ct.Th)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Total Area of Inner and Outer Cortices (Ct.Ar)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Trabecular Number (Tb.N)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Cancellous Adjusted Apposition Rate (Cn.AjAR)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Endocortical Osteoid Thickness (Ec.O.Th)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Endocortical Bone Mineral Apposition Rate (Ec.MAR)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Endocortical Osteoid Surface / Bone Surface (Ec.OS/BS)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Total Area of Cortical Porosity (Ct.Po.Ar)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Cancellous Eroded Surface / Bone Surface (Cn.ES/BS)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Endocortical Eroded Surface / Bone Surface (Ec.ES/BS)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Endocortical Adjusted Apposition Rate (Ec.AjAR)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Intracortical Bone Mineral Apposition Rate (Ic.MAR)(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(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(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Intracortical Osteoid Thickness (Ic.O.Th)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Intracortical Osteoid Surface / Bone Surface (Ic.OS/BS)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Intracortical Eroded Surface / Bone Surface (Ic.ES/BS)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Change in Intracortical Adjusted Apposition Rate (Ic.AjAR)(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Raw Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA(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 Emotional Role Limitations Domain(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(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Raw 1/3 Radius Bone Mineralization Density (BMD) Assessed by DXA.(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(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(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))
- Perceived Interference (PI) of the Fatigue Symptom Inventory (FSI)(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))
- Average Severity Score of the Fatigue Symptom Inventory (FSI)(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 Mental Health Domain(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 Low From the Back-Scattered Electron Imaging of Bone-Biopsies(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- Raw Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA(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))
- Composite Severity Score of the Fatigue Symptom Inventory (FSI)(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 AP Spine Bone Mineralization Density (BMD) Assessed by DXA(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(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(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(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 Osteocalcin(Baseline, 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 High From the Back-Scattered Electron Imaging of Bone-Biopsies(Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies)
- SF36 General Health Domain(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(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(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))
- Number of Participants With Nephrolithiasis/Nephrocalcinosis(Baseline, 12-Month Visit, 24-Month Visit, 36-Month Visit, 48-Month Visit, and 60-Month Visit)
- SF36 Vitality Domain(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 Alkaline Phosphatase(Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH))
- Serum Calcium(Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH))
- 24 Hour Urine NTX Telopeptide(Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH))
- Serum Phosphorus(Baseline, 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(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(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.(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 AP Spine Bone Mineralization Density (BMD) Assessed by DXA(Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits)
- Z-score of Femoral Neck Bone Mineralization Density (BMD) Assessed by DXA(Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits)
- Z-score of Lateral Spine Bone Mineralization Density (BMD) Assessed by DXA(Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits)
- Z-score of Total Hip Bone Mineralization Density (BMD) Assessed by DXA(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(Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits)