Ignite Creation Date:
2024-05-05 @ 5:08 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00395538
Status:
TERMINATED
Last Update Posted:
2019-08-28
First Post:
2006-11-02
Brief Title:
Effects of PTH Replacement on Bone in Hypoparathyroidism
Sponsor:
National Institute of Dental and Craniofacial Research NIDCR
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Effects of PTH Replacement on Bone in Hypoparathyroidism
Status:
TERMINATED
Status Verified Date:
2019-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Pharmacy temporarily suspended by FDA
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
Detailed Description:
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 hypoparathyroidismTAB
Design
This study will treat hypoparathyroid individuals with synthetic human PTH 1-34 HPTH 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
With respect to HPTH treatment this study is a single group within-subjects repeated measures treatment trial With respect to all bone biopsy analyses the design is a parallel group design with each subject allocated to one of the 3 biopsy follow-up times 1 2 or 4 years after initiation of HPTH therapy Post-baseline biopsy timing will be randomly assigned 11214 respectively to each subject stratified by gender and by menopausal status when relevant Changes from baseline time 0 to 1 2 and 4-years will be compared Subjects who were on conventional therapy in the former version of the protocol will also be randomized into the new study design In contrast to new subjects whose biopsy is performed at the end of the conventional care run-in period the pre-conventional care biopsy will be used as the baseline for the those subjects entering the new design after having been on conventional care in the older protocol Because it is not known with certainty what effects duration of time on conventional therapy will have on biopsy results randomization will also be stratified on status of prior study participation The subjects who were on HPTH therapy at the time of the protocol redesign are followed as a separate group under this protocol
Outcome Measures
Primary
Changes in static and dynamic bone histomorphometry after 1 year 2 years and 4 years of HPTH therapy Primary outcome measurements include
Mineralized perimeter
Bone formation rate
Cortical width
Cortical area
Osteoid width
Osteoid perimeter
Mineral apposition rate
Secondary
Changes in bone mineralization density distribution at 1 2 and 4 years of HPTH therapy The specific outcomes that will be measured include
Spectral calcium-mean
Calcium-peak
Calcium-width
Changes from baseline will be assessed in the following outcomes
Biochemical markers of bone metabolism osteocalcin bone-specific alkaline phosphatase collagen cross-linked N-telopeptide
Serum and urine calcium 125-OH2-Vitamin D
Bone density assessed by DXA and quantitative CT
Nephrocalcinosis by ultrasound and CT
Fatigue Symptom Inventory
6-Minute Walk Test
SF-36 Health Survey
Tertiary
Changes in blood chemistries and FGF23 renal mineral handling and PTH sensitivity with the initiation of HPTH which include
Serum albumin calcium phosphorus magnesium sodium potassium chloride Total CO2 creatinine glucose urea nitrogen and FGF23
Urine cAMP creatinine phosphorus calcium and pH
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 hypoparathyroidismTAB
Design
This study will treat hypoparathyroid individuals with synthetic human PTH 1-34 HPTH 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
With respect to HPTH treatment this study is a single group within-subjects repeated measures treatment trial With respect to all bone biopsy analyses the design is a parallel group design with each subject allocated to one of the 3 biopsy follow-up times 1 2 or 4 years after initiation of HPTH therapy Post-baseline biopsy timing will be randomly assigned 11214 respectively to each subject stratified by gender and by menopausal status when relevant Changes from baseline time 0 to 1 2 and 4-years will be compared Subjects who were on conventional therapy in the former version of the protocol will also be randomized into the new study design In contrast to new subjects whose biopsy is performed at the end of the conventional care run-in period the pre-conventional care biopsy will be used as the baseline for the those subjects entering the new design after having been on conventional care in the older protocol Because it is not known with certainty what effects duration of time on conventional therapy will have on biopsy results randomization will also be stratified on status of prior study participation The subjects who were on HPTH therapy at the time of the protocol redesign are followed as a separate group under this protocol
Outcome Measures
Primary
Changes in static and dynamic bone histomorphometry after 1 year 2 years and 4 years of HPTH therapy Primary outcome measurements include
Mineralized perimeter
Bone formation rate
Cortical width
Cortical area
Osteoid width
Osteoid perimeter
Mineral apposition rate
Secondary
Changes in bone mineralization density distribution at 1 2 and 4 years of HPTH therapy The specific outcomes that will be measured include
Spectral calcium-mean
Calcium-peak
Calcium-width
Changes from baseline will be assessed in the following outcomes
Biochemical markers of bone metabolism osteocalcin bone-specific alkaline phosphatase collagen cross-linked N-telopeptide
Serum and urine calcium 125-OH2-Vitamin D
Bone density assessed by DXA and quantitative CT
Nephrocalcinosis by ultrasound and CT
Fatigue Symptom Inventory
6-Minute Walk Test
SF-36 Health Survey
Tertiary
Changes in blood chemistries and FGF23 renal mineral handling and PTH sensitivity with the initiation of HPTH which include
Serum albumin calcium phosphorus magnesium sodium potassium chloride Total CO2 creatinine glucose urea nitrogen and FGF23
Urine cAMP creatinine phosphorus calcium and pH
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 07-D-0016 | None | None | None |