OsteoporosisPhase 1NCT01333267
One Week Comparison Study of PTH and PTHrP Infusions
A Phase 1 study testing Parathyroid Hormone-related Protein (1-36), parathyroid hormone (1-34) and PTH (1-34) and PTHrP (1-36) in people with Osteoporosis and Hypercalcemia of Malignancy, run by University of Pittsburgh at 1 site in United States.
Trial summary
This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, or Parathyroid Hormone, PTH, that can be given safely over one week in healthy African-American volunteers. Read more about this study
- Who is it for?
- Ages 24 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Osteoporosis, Hypercalcemia of Malignancy, Hyperparathyroidism
- What is being tested?
- Parathyroid Hormone-related Protein (1-36), parathyroid hormone (1-34) and PTH (1-34) and PTHrP (1-36)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Jul 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy African-American subjects of both sexes between the ages of 24-35 years, who are able to spend one week on the Clinical \& Translational Research Center (CTRC) at the University of Pittsburgh Medical Center (UPMC) Montefiore.
Who cannot join
- Subjects with cardiac, vascular, renal (serum creatinine > 1.5), pulmonary, endocrine, musculoskeletal, hepatic, hematologic, malignant, or rheumatologic disease will be excluded.
- Those found to have vitamin D deficiency, defined as a 25-OH vitamin D level < 10 ng/mL will also be excluded.
- Additionally, those with BMI > 30, anemia (hematocrit < 36% in women, <40% in men), significant alcohol use, illicit drug use, hypertension (BP>160/90), or baseline hypotension (systolic blood pressure < 90mmHg) will be excluded.
- Those taking chronic medications (except oral contraceptive pills (OCP's) or stable doses of thyroid replacement) or those who have received an investigational drug in the past 90 days will also be excluded.
- Prior participants in PTH or PTHrP studies will not be eligible to participate.
- Additionally pregnant women and lactating women will be excluded; all women will have a urine pregnancy test performed immediately before starting the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Comparison of Skeletal and Mineral Metabolism Responses in Healthy African-Americans and Caucasians Using a Continuous Seven-Day Parathyroid Hormone (PTH) or Parathyroid Hormone-related Protein (PTHrP) Infusion
This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, or Parathyroid Hormone, PTH, that can be given safely over one week in healthy African-American volunteers. The investigators plan to infuse low doses of intravenous PTHrP or PTH to determine if it leads to a sustained and progressive suppression of bone formation as occurs in humoral hypercalcemia of malignancy (HHM) or an increase in bone formation as occurs in hyperparathyroidism (HPT). Additionally, the investigators will assess the direct influence of PTHrP and PTH on vitamin D metabolism, markers of bone turnover, and fractional excretion of calcium. These results will be compared to previous studies of Caucasian volunteers.
Read the detailed description
This study will expand upon earlier infusion studies in healthy Caucasian and Asian volunteers in which continuous infusions of PTH and PTHrP were given for six-, 12-, and 48 hours. These studies demonstrated: 1) There is a dose-related increase in 1,25 (OH)2 vitamin D in response to PTHrP and PTH over multiple days. 2) There is a markedly attenuated vitamin D response to PTHrP compared to PTH, particularly during the second 24 hours. 3) The increase in 1,25 (OH)2 vitamin D is almost certainly responsible for the greater calcemic effect of PTH compared to PTHrP. 4) PTHrP is obviously a weaker agonist of 1,25 (OH)2 vitamin D but does not result in its suppression as is seen in Humoral Hypercalcemia of Malignancy (HHM). Thus, the suppression of 1,25 (OH)2 vitamin D seen in HHM remains unexplained. In addition to assessing the effects of an infusion of PTHrP and PTH on calcium handling and 1,25 (OH)2 vitamin D, we also measured their effects on markers of bone turnover. Given the clinical observations seen in primary hyperparathyroidism (HPT) and HHM, we anticipated that PTH would stimulate both bone resorption and formation, while PTHrP would stimulate bone resorption but inhibit formation. However, we observed that infusions of PTHrP and PTH resulted in an equivalent, rapid increase in bone resorption as measured by N-telopeptide (NTx) and C-telopeptide (CTx), as well as a progressive decline in bone formation. There was no difference between PTH and PTHrP. Because of these findings, it was surmised that infusions of a longer duration would lead to an increase in bone formation and 1,25 (OH)2D production with both peptides, as is seen in HPT. Very recently, we have completed a seven-day infusion model in healthy Caucasian and Asian volunteers to test this hypothesis (J. Bone Min. Res., 2011). A total of 22 individuals were given either seven-day infusions of PTH or PTHrP, and maximal safe doses were found to be 2 and 4 picomoles (pmol)/kg/hour, respectively, lower than the doses used in previous, briefer infusion studies. All patients developed sustained but very mild hypercalcemia (mean = 10.3 mg/dL) and hypercalciuria with rapid increase in bone resorption. Surprisingly, bone formation again was suppressed for the entire seven days with a robust rebound in bone formation on cessation of the respective peptide. This is consistent with what may occur during lactation and HHM, but again contrary to what occurs in HPT.
The previous infusion studies were done only in Caucasian and Asian volunteers as there are extensively documented physiologic differences in bone metabolism between African-Americans and Caucasians. Much of the racial differences noted in bone metabolism come from the osteoporosis literature. African-Americans are known to have higher bone mineral densities (BMD) and to be at lower risk of developing fragility fractures. There are many factors which may explain these racial differences in bone metabolism, including altered calcium economy, vitamin D differences, peak attained bone mass, muscle mass and obesity, mechanism of falls, remodeling rates, bone micro-architecture, hip axis geometry, and other unknown hereditary differences. It is also well established that African-Americans on average, have lower 25-OH vitamin D concentrations and thus higher PTH levels. Despite elevations in PTH, there is paradoxically no increase in bone loss indicating that a relative skeletal resistance to PTH may exist. We hope that by performing this seven-day infusion protocol in healthy African-American volunteers we can learn more about racial differences in bone turnover, renal calcium, PTH concentrations, vitamin D metabolism, and skeletal responses to lactation in this under-studied population.
Ninety healthy African-American men and women will be screened for an eight-day inpatient admission to the Clinical \& Translational Research Center (CTRC). Sixty evaluable research participants will receive a seven day infusion of a predetermined dose of either PTHrP or PTH. Vital signs and blood and urine tests will be monitored frequently as per the study flow sheet. The starting dose of either peptide, 2 picomoles (pmols)/kg, will be given to three normal healthy subjects. Via a dose escalation protocol, the dose will be escalated in increments with successive groups of three subjects each, until early adverse effects (mild hypercalcemia, postural hypotension, tachycardia) are seen. This determined safe dose will then be given to 10 subjects. This dose escalation study design has been used in several prior studies at this institution in order to achieve a sustained mild serum hypercalcemia in the 10.5-11 mg/dL range in research studies. The investigators with this study are trying to determine a safe dose of PTHrP and PTH in African-American volunteers and determining if this population has the same physiologic response as Caucasians.
Subject population will consist of healthy young African-American adults, ages 24-35. It is anticipated that we will need to screen 90 patients in order to obtain 60 evaluable subjects.
- Being tested
- Parathyroid Hormone-related Protein (1-36), parathyroid hormone (1-34), PTH (1-34) and PTHrP (1-36)
- Keywords
- Endocrine System Diseases, MusculoSkeletal System Disease, Hormones, Postmenopausal Women, Bone metabolism, Physiologic Properties, African-Americans
- Medical subject headings
- Osteoporosis, Humoral Hypercalcemia Of Malignancy, Hyperparathyroidism, Bone Diseases, Endocrine, Endocrine System Diseases, Musculoskeletal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Parathyroid Hormone-related Protein (1-36)Drug
Also called PTHrP(1-36), Bone anabolic agents
PTHrP (1-36) intravenously at 2 picomoles (pmols)/kg/hr for one week; doses will be increased by 2 picomoles (pmols)/kg/hr in subsequent subjects.
parathyroid hormone (1-34)Drug
Also called PTH(1-34), Bone anabolic agent
PTH (1-34) intravenously at 2 picomoles (pmols)/kg/hr for one week; doses will be increased by 2 picomoles (pmols)/kg/hr in subsequent subjects.
PTH (1-34) and PTHrP (1-36)Drug
Also called Parathyroid Hormone-related Protein (1-36), PTHrP(1-36), IND 49,175, Parathyroid Hormone (1-34)
This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, or Parathyroid Hormone, PTH, that can be given safely over one week in healthy African-American volunteers. The investigators plan to infuse low doses of intravenous PTHrP or PTH to determine if it leads to a sustained and progressive suppression of bone formation as occurs in humoral hypercalcemia of malignancy (HHM) or an increase in bone formation as occurs in hyperparathyroidism (HPT). Additionally, the investigators will assess the direct influence of PTHrP and PTH on vitamin D metabolism, markers of bone turnover, and fractional excretion of calcium.
| Study group | Role | What they receive |
|---|---|---|
| PTHrP group | Experimental | Subjects receive PTHrP(1-36) starting with doses of 2 picomoles (pmols)/kg/hr for one week. Subsequent dosing groups are determined by the response to PTHrP doses. Receives: Drug: Parathyroid Hormone-related Protein (1-36); Drug: PTH (1-34) and PTHrP (1-36) |
| PTH dosing group | Experimental | Subjects receive PTH(1-34) starting with doses of 2 picomoles (pmols)/kg/hr for one week. Subsequent dosing groups are determined by the response to PTH doses. Receives: Drug: parathyroid hormone (1-34); Drug: PTH (1-34) and PTHrP (1-36) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: The absence of any dose limiting toxicity (DLT) criteria consisting of one major criteria or two minor criteria.
Measured: one week
Secondary outcomes (1)
Blood collections analyzed for measurements of PTH(1-34), PTH(1-84), 25-OH vitamin D, 1,25(OH)2 vitamin D, markers of bone metabolism, and fractional excretion of calcium measurements.
Measured: one week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2011 (estimated)
- Study startJan 2015
- Primary completionJul 2017 (estimated)
- Study completionJul 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (52)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mara Horwitz, University of Pittsburgh
- Investigators
- Mara J. Horwitz, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01333267
- Sponsor's protocol ID
- PRO10060214
- Status last verified
- Dec 2014
- First submitted
- 8 Apr 2011
- Last updated
- 5 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dean T, Vilardaga JP, Potts JT Jr, Gardella TJ. Altered selectivity of parathyroid hormone (PTH) and PTH-related protein (PTHrP) for distinct conformations of the PTH/PTHrP receptor. Mol Endocrinol. 2008 Jan;22(1):156-66. doi: 10.1210/me.2007-0274. Epub 2007 Sep 13.
PubMed 17872377Horwitz MJ, Tedesco MB, Sereika SM, Syed MA, Garcia-Ocana A, Bisello A, Hollis BW, Rosen CJ, Wysolmerski JJ, Dann P, Gundberg C, Stewart AF. Continuous PTH and PTHrP infusion causes suppression of bone formation and discordant effects on 1,25(OH)2 vitamin D. J Bone Miner Res. 2005 Oct;20(10):1792-803. doi: 10.1359/JBMR.050602. Epub 2005 Jun 6.
PubMed 16160737Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocana A, Stewart AF. Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers. J Clin Endocrinol Metab. 2003 Apr;88(4):1603-9. doi: 10.1210/jc.2002-020773.
PubMed 12679445Nelson DA, Jacobsen G, Barondess DA, Parfitt AM. Ethnic differences in regional bone density, hip axis length, and lifestyle variables among healthy black and white men. J Bone Miner Res. 1995 May;10(5):782-7. doi: 10.1002/jbmr.5650100515.
PubMed 7639113George A, Tracy JK, Meyer WA, Flores RH, Wilson PD, Hochberg MC. Racial differences in bone mineral density in older men. J Bone Miner Res. 2003 Dec;18(12):2238-44. doi: 10.1359/jbmr.2003.18.12.2238.
PubMed 14672360Kalkwarf HJ, Zemel BS, Gilsanz V, Lappe JM, Horlick M, Oberfield S, Mahboubi S, Fan B, Frederick MM, Winer K, Shepherd JA. The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race. J Clin Endocrinol Metab. 2007 Jun;92(6):2087-99. doi: 10.1210/jc.2006-2553. Epub 2007 Feb 20.
PubMed 17311856Hui SL, Dimeglio LA, Longcope C, Peacock M, McClintock R, Perkins AJ, Johnston CC Jr. Difference in bone mass between black and white American children: attributable to body build, sex hormone levels, or bone turnover? J Clin Endocrinol Metab. 2003 Feb;88(2):642-9. doi: 10.1210/jc.2002-020653.
PubMed 12574194Bachrach LK, Hastie T, Wang MC, Narasimhan B, Marcus R. Bone mineral acquisition in healthy Asian, Hispanic, black, and Caucasian youth: a longitudinal study. J Clin Endocrinol Metab. 1999 Dec;84(12):4702-12. doi: 10.1210/jcem.84.12.6182.
PubMed 10599739Gilsanz V, Skaggs DL, Kovanlikaya A, Sayre J, Loro ML, Kaufman F, Korenman SG. Differential effect of race on the axial and appendicular skeletons of children. J Clin Endocrinol Metab. 1998 May;83(5):1420-7. doi: 10.1210/jcem.83.5.4765.
PubMed 9589632Abrams SA, O'brien KO, Liang LK, Stuff JE. Differences in calcium absorption and kinetics between black and white girls aged 5-16 years. J Bone Miner Res. 1995 May;10(5):829-33. doi: 10.1002/jbmr.5650100521.
PubMed 7639119Gilsanz V, Roe TF, Mora S, Costin G, Goodman WG. Changes in vertebral bone density in black girls and white girls during childhood and puberty. N Engl J Med. 1991 Dec 5;325(23):1597-600. doi: 10.1056/NEJM199112053252302.
PubMed 1944449Luckey MM, Wallenstein S, Lapinski R, Meier DE. A prospective study of bone loss in African-American and white women--a clinical research center study. J Clin Endocrinol Metab. 1996 Aug;81(8):2948-56. doi: 10.1210/jcem.81.8.8768857.
PubMed 8768857Thomas PA. Racial and ethnic differences in osteoporosis. J Am Acad Orthop Surg. 2007;15 Suppl 1:S26-30. doi: 10.5435/00124635-200700001-00008.
PubMed 17766786Han ZH, Palnitkar S, Rao DS, Nelson D, Parfitt AM. Effects of ethnicity and age or menopause on the remodeling and turnover of iliac bone: implications for mechanisms of bone loss. J Bone Miner Res. 1997 Apr;12(4):498-508. doi: 10.1359/jbmr.1997.12.4.498.
PubMed 9101361Cauley JA, Wampler NS, Barnhart JM, Wu L, Allison M, Chen Z, Hendrix S, Robbins J, Jackson RD; Women's Health Initiative Observational Study. Incidence of fractures compared to cardiovascular disease and breast cancer: the Women's Health Initiative Observational Study. Osteoporos Int. 2008 Dec;19(12):1717-23. doi: 10.1007/s00198-008-0634-y. Epub 2008 Jul 16.
PubMed 18629572
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Skeletal and Mineral Metabolism Responses in Healthy African-Americans and Caucasians Using a Continuous Seven-Day Parathyroid Hormone (PTH) or Parathyroid Hormone-related Protein (PTHrP) Infusion
- ClinicalTrials.gov ID
- NCT01333267
- Acronym / sponsor ID
- PRO10060214
- Keywords
- Endocrine System Diseases, MusculoSkeletal System Disease, Hormones, Postmenopausal Women, Bone metabolism, Physiologic Properties, African-Americans
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Jul 2017 (estimated)
- Study completion
- Jul 2017 (estimated)
- First posted
- 11 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, or Parathyroid Hormone, PTH, that can be given safely over one week in healthy African-American volunteers. The investigators plan to infuse low doses of intravenous PTHrP or PTH to determine if it leads to a sustained and progressive suppression of bone formation as occurs in humoral hypercalcemia of malignancy (HHM) or an increase in bone formation as occurs in hyperparathyroidism (HPT). Additionally, the investigators will assess the direct influence of PTHrP and PTH on vitamin D metabolism, markers of bone turnover, and fractional excretion of calcium. These results will be compared to previous studies of Caucasian volunteers.
Detailed description
This study will expand upon earlier infusion studies in healthy Caucasian and Asian volunteers in which continuous infusions of PTH and PTHrP were given for six-, 12-, and 48 hours. These studies demonstrated: 1) There is a dose-related increase in 1,25 (OH)2 vitamin D in response to PTHrP and PTH over multiple days. 2) There is a markedly attenuated vitamin D response to PTHrP compared to PTH, particularly during the second 24 hours. 3) The increase in 1,25 (OH)2 vitamin D is almost certainly responsible for the greater calcemic effect of PTH compared to PTHrP. 4) PTHrP is obviously a weaker agonist of 1,25 (OH)2 vitamin D but does not result in its suppression as is seen in Humoral Hypercalcemia of Malignancy (HHM). Thus, the suppression of 1,25 (OH)2 vitamin D seen in HHM remains unexplained. In addition to assessing the effects of an infusion of PTHrP and PTH on calcium handling and 1,25 (OH)2 vitamin D, we also measured their effects on markers of bone turnover. Given the clinical observations seen in primary hyperparathyroidism (HPT) and HHM, we anticipated that PTH would stimulate both bone resorption and formation, while PTHrP would stimulate bone resorption but inhibit formation. However, we observed that infusions of PTHrP and PTH resulted in an equivalent, rapid increase in bone resorption as measured by N-telopeptide (NTx) and C-telopeptide (CTx), as well as a progressive decline in bone formation. There was no difference between PTH and PTHrP. Because of these findings, it was surmised that infusions of a longer duration would lead to an increase in bone formation and 1,25 (OH)2D production with both peptides, as is seen in HPT. Very recently, we have completed a seven-day infusion model in healthy Caucasian and Asian volunteers to test this hypothesis (J. Bone Min. Res., 2011). A total of 22 individuals were given either seven-day infusions of PTH or PTHrP, and maximal safe doses were found to be 2 and 4 picomoles (pmol)/kg/hour, respectively, lower than the doses used in previous, briefer infusion studies. All patients developed sustained but very mild hypercalcemia (mean = 10.3 mg/dL) and hypercalciuria with rapid increase in bone resorption. Surprisingly, bone formation again was suppressed for the entire seven days with a robust rebound in bone formation on cessation of the respective peptide. This is consistent with what may occur during lactation and HHM, but again contrary to what occurs in HPT.
The previous infusion studies were done only in Caucasian and Asian volunteers as there are extensively documented physiologic differences in bone metabolism between African-Americans and Caucasians. Much of the racial differences noted in bone metabolism come from the osteoporosis literature. African-Americans are known to have higher bone mineral densities (BMD) and to be at lower risk of developing fragility fractures. There are many factors which may explain these racial differences in bone metabolism, including altered calcium economy, vitamin D differences, peak attained bone mass, muscle mass and obesity, mechanism of falls, remodeling rates, bone micro-architecture, hip axis geometry, and other unknown hereditary differences. It is also well established that African-Americans on average, have lower 25-OH vitamin D concentrations and thus higher PTH levels. Despite elevations in PTH, there is paradoxically no increase in bone loss indicating that a relative skeletal resistance to PTH may exist. We hope that by performing this seven-day infusion protocol in healthy African-American volunteers we can learn more about racial differences in bone turnover, renal calcium, PTH concentrations, vitamin D metabolism, and skeletal responses to lactation in this under-studied population.
Ninety healthy African-American men and women will be screened for an eight-day inpatient admission to the Clinical \& Translational Research Center (CTRC). Sixty evaluable research participants will receive a seven day infusion of a predetermined dose of either PTHrP or PTH. Vital signs and blood and urine tests will be monitored frequently as per the study flow sheet. The starting dose of either peptide, 2 picomoles (pmols)/kg, will be given to three normal healthy subjects. Via a dose escalation protocol, the dose will be escalated in increments with successive groups of three subjects each, until early adverse effects (mild hypercalcemia, postural hypotension, tachycardia) are seen. This determined safe dose will then be given to 10 subjects. This dose escalation study design has been used in several prior studies at this institution in order to achieve a sustained mild serum hypercalcemia in the 10.5-11 mg/dL range in research studies. The investigators with this study are trying to determine a safe dose of PTHrP and PTH in African-American volunteers and determining if this population has the same physiologic response as Caucasians.
Subject population will consist of healthy young African-American adults, ages 24-35. It is anticipated that we will need to screen 90 patients in order to obtain 60 evaluable subjects.
Study design
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PTHrP group | Experimental | Drug: Parathyroid Hormone-related Protein (1-36), Drug: PTH (1-34) and PTHrP (1-36)Subjects receive PTHrP(1-36) starting with doses of 2 picomoles (pmols)/kg/hr for one week. Subsequent dosing groups are determined by the response to PTHrP doses. |
| PTH dosing group | Experimental | Drug: parathyroid hormone (1-34), Drug: PTH (1-34) and PTHrP (1-36)Subjects receive PTH(1-34) starting with doses of 2 picomoles (pmols)/kg/hr for one week. Subsequent dosing groups are determined by the response to PTH doses. |
Who may qualify
- Ages
- 24 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy African-American subjects of both sexes between the ages of 24-35 years, who are able to spend one week on the Clinical \& Translational Research Center (CTRC) at the University of Pittsburgh Medical Center (UPMC) Montefiore.
Key exclusion criteria (6 listed)
- Subjects with cardiac, vascular, renal (serum creatinine > 1.5), pulmonary, endocrine, musculoskeletal, hepatic, hematologic, malignant, or rheumatologic disease will be excluded.
- Those found to have vitamin D deficiency, defined as a 25-OH vitamin D level < 10 ng/mL will also be excluded.
- Additionally, those with BMI > 30, anemia (hematocrit < 36% in women, <40% in men), significant alcohol use, illicit drug use, hypertension (BP>160/90), or baseline hypotension (systolic blood pressure < 90mmHg) will be excluded.
- Those taking chronic medications (except oral contraceptive pills (OCP's) or stable doses of thyroid replacement) or those who have received an investigational drug in the past 90 days will also be excluded.
- Prior participants in PTH or PTHrP studies will not be eligible to participate.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Parathyroid Hormone-related Protein (1-36)Also: PTHrP(1-36), Bone anabolic agentsPTHrP (1-36) intravenously at 2 picomoles (pmols)/kg/hr for one week; doses will be increased by 2 picomoles (pmols)/kg/hr in subsequent subjects. | Drug | PTHrP group |
| parathyroid hormone (1-34)Also: PTH(1-34), Bone anabolic agentPTH (1-34) intravenously at 2 picomoles (pmols)/kg/hr for one week; doses will be increased by 2 picomoles (pmols)/kg/hr in subsequent subjects. | Drug | PTH dosing group |
| PTH (1-34) and PTHrP (1-36)Also: Parathyroid Hormone-related Protein (1-36), PTHrP(1-36), IND 49,175, Parathyroid Hormone (1-34)This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, or Parathyroid Hormone, PTH, that can be given safely over one week in healthy African-American volunteers. The investigators plan to infuse low doses of intravenous PTHrP or PTH to determine if it leads to a sustained and progressive suppression of bone formation as occurs in humoral hypercalcemia of malignancy (HHM) or an increase in bone formation as occurs in hyperparathyroidism (HPT). Additionally, the investigators will assess the direct influence of PTHrP and PTH on vitamin D metabolism, markers of bone turnover, and fractional excretion of calcium. | Drug | PTH dosing group, PTHrP group |
Primary outcome
Safety: The absence of any dose limiting toxicity (DLT) criteria consisting of one major criteria or two minor criteria.
Time frame: one week
1 secondary outcome
Blood collections analyzed for measurements of PTH(1-34), PTH(1-84), 25-OH vitamin D, 1,25(OH)2 vitamin D, markers of bone metabolism, and fractional excretion of calcium measurements.
Time frame: one week
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2014.
- Background: PubMed 17872377Dean T, Vilardaga JP, Potts JT Jr, Gardella TJ. Altered selectivity of parathyroid hormone (PTH) and PTH-related protein (PTHrP) for distinct conformations of the PTH/PTHrP receptor. Mol Endocrinol. 2008 Jan;22(1):156-66. doi: 10.1210/me.2007-0274. Epub 2007 Sep 13.
- Background: PubMed 16160737Horwitz MJ, Tedesco MB, Sereika SM, Syed MA, Garcia-Ocana A, Bisello A, Hollis BW, Rosen CJ, Wysolmerski JJ, Dann P, Gundberg C, Stewart AF. Continuous PTH and PTHrP infusion causes suppression of bone formation and discordant effects on 1,25(OH)2 vitamin D. J Bone Miner Res. 2005 Oct;20(10):1792-803. doi: 10.1359/JBMR.050602. Epub 2005 Jun 6.
- Background: PubMed 12679445Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocana A, Stewart AF. Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers. J Clin Endocrinol Metab. 2003 Apr;88(4):1603-9. doi: 10.1210/jc.2002-020773.
- Background: PubMed 7639113Nelson DA, Jacobsen G, Barondess DA, Parfitt AM. Ethnic differences in regional bone density, hip axis length, and lifestyle variables among healthy black and white men. J Bone Miner Res. 1995 May;10(5):782-7. doi: 10.1002/jbmr.5650100515.
- Background: PubMed 14672360George A, Tracy JK, Meyer WA, Flores RH, Wilson PD, Hochberg MC. Racial differences in bone mineral density in older men. J Bone Miner Res. 2003 Dec;18(12):2238-44. doi: 10.1359/jbmr.2003.18.12.2238.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mara J. Horwitz, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Parathyroid Hormone-related Protein (1-36), parathyroid hormone (1-34) and PTH (1-34) and PTHrP (1-36) in people with Osteoporosis and Hypercalcemia of Malignancy, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: The absence of any dose limiting toxicity (DLT) criteria consisting of one major criteria or two minor criteria. (time frame: one week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01333267, which also lists 52 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2014.