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OsteoporosisEarly Phase 1NCT00580788

One Week Parathyroid Hormone-related Protein (PTHrP) IV Dose Escalation Study

A Early Phase 1 study testing PTHrP (1-36) in people with Osteoporosis and Humoral Hypercalcemia of Malignancy, run by University of Pittsburgh at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, that can be given safely over one week. The investigators plan to infuse low doses of intravenous PTHrP to determine if it leads to a sustained and progressive suppression of bone formation as occurs… Read more about this study

Who is it for?
Ages 24 to 35 yearsHealthy volunteers can take part
What is being tested?
PTHrP (1-36)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
Jan 2008to Dec 2009
Phase
Early Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 caucasian subjects of both sexes between the ages of 24-35 years, who are able to spend one week on the Clinical \& Translational Research Center at the University of Pittsburgh Medical Center (UPMC) Montefiore

Who cannot join

  • Pregnancy
  • Any cardiac, renal, pulmonary, endocrine, musculoskeletal, hepatic, hematological, malignant or rheumatologic diseases
  • Body mass index great than 30
  • Anemia
  • Significant alcohol or drug abuse
  • Baseline hypotension or hypertension
Show all 11Show fewer
  • Abnormal screening labs
  • Use of certain chronic medications excluding oral contraceptives
  • Receiving an investigational drug in the last 90 days
  • Previously receiving PTH or PTHrP
  • African-American race

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

Official title: Determining the Maximal Safe Dose of a Continuous Infusion of Parathyroid Hormone-related Protein(1-36): Effects on Bone Formation

This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, that can be given safely over one week. The investigators plan to infuse low doses of intravenous PTHrP 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 on markers of bone turnover, and plasma 1,25 (OH)2 vitamin D regulation in healthy human volunteers.

Read the detailed description

During this research the investigators administer PTHrP to healthy young volunteers in a controlled, continuous intravenous manner. As research subjects complete the week-long study without adverse effects, the dose of PThrP will be increased in later subjects. In the event of a significant adverse effect, immediate action will be taken to reverse it. The investigators want to estimate the effect of a sustainable level of mild hypercalcemia achieved by a week-long intravenous infusion of PTHrP has on vitamin D metabolism, markers of bone turnover and fractional excretion of calcium.

Being tested
PTHrP (1-36)
Keywords
Endocrine System Diseases, MusculoSkeletal System Diseases, Hormones, Malignancy, Postmenopausal Women, Bone metabolism
Medical subject headings
Osteoporosis, Humoral Hypercalcemia Of Malignancy, Hyperparathyroidism, Endocrine System Diseases, Musculoskeletal Diseases, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PTHrP (1-36)Drug

    Also called Parathyroid Hormone-related Protein (1-36)

    IND # 49,175

Study groups in NCT00580788
Study groupRoleWhat they receive
PTHrP(1-36) 2 pmol/kg/hrExperimentalPTHrP(1-36) at 2 picomoles/kg/hr for one week.
Receives: Drug: PTHrP (1-36)
PTHrP (1-36) 4 pmol/kg/hrExperimentalPTHrP(1-36) at 4 picomoles/kg/hr for one week.
Receives: Drug: PTHrP (1-36)
PTHrP(1-36) 5 pmol/kg/hrExperimentalPTHrP(1-36) at 5 picomoles/kg/hr for one week.
Receives: Drug: PTHrP (1-36)
PTHrP(1-36) 6 pmol/kg/hrExperimentalPTHrP(1-36) at 6 picomoles/kg/hr for one week.
Receives: Drug: PTHrP (1-36)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicity (DLT)

    DLT was defined as achieving one major criterion or two minor criteria rated at ≥ 2 on a scale of 0-5. The major criteria were defined as symptomatic orthostatic hypotension (systolic BP fall >30 mm/hg), tachycardia (pulse > 120), hypertension (systolic BP >160 mm/hg on 2 occasions), hypercalcemia (serum calcium ≥ 12 mg/dl), and hypophosphatemia (serum phosphorous < 1.5 mg/dl). Minor criteria included symptoms such as flushing, nausea, abdominal or muscle cramps, dizziness, lightheadedness, palpitations, etc.

    Measured: 12 hours after the infusion was started then q 8 hours for 7 days

  2. Total Serum Calcium

    mg/dl

    Measured: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete

  3. Ionized Serum Calcium

    mg/dl

    Measured: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete

  4. Serum Phosphorous

    mg/dl

    Measured: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete

Secondary outcomes (9)
  1. 1,25 Vitamin D

    pg/ml

    Measured: Baseline and Daily through day 8 then at follow-up visit

  2. 24 Hour Urine Calcium

    mg/gm creatinine collected on day 7 of PTHrP infusion

    Measured: 24 hours

  3. Tubular Maximum of Phosphorous (TmP/GFR)

    mg/dl calculated from daily second morning void

    Measured: daily

  4. Serum Amino-terminal Telopeptide of Collagen -1 (sNTX)

    % change from baseline

    Measured: Baseline, Daily, and 1 week follow-up

  5. Serum Carboxy-terminal Telopeptide of Collagen -1 (sCTX)

    % change from baseline

    Measured: Baseline, Daily, and 1 week follow-up

  6. Amino-terminal Peptides of Procollagen 1 (P1NP)

    % change from baseline

    Measured: Baseline, Daily, and 1 week follow-up

  7. Bone Specific Alkaline Phosphatase (BSAP)

    % change from baseline

    Measured: Baseline, Daily, and 1 week follow-up

  8. Parathyroid Hormone (1-84)

    pg/ml

    Measured: Baseline and Daily

  9. Fractional Excretion of Calcium

    % calculated from daily second morning void

    Measured: daily

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Dec 2007 (estimated)
  2. Study startJan 2008
  3. Primary completionDec 2009
  4. Study completionDec 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Allocation
Non-randomised
Intervention model
Single group
Masking
Single blind
Who is masked
Participant
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00580788
Sponsor's protocol ID
PRO07040081
Other IDs
R01DK073039
Status last verified
Feb 2016
First submitted
20 Dec 2007
Last updated
11 Feb 2016
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Juppner H, Abou-Samra AB, Freeman M, Kong XF, Schipani E, Richards J, Kolakowski LF Jr, Hock J, Potts JT Jr, Kronenberg HM, et al. A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Science. 1991 Nov 15;254(5034):1024-6. doi: 10.1126/science.1658941.

    PubMed 1658941
  • Orloff JJ, Wu TL, Heath HW, Brady TG, Brines ML, Stewart AF. Characterization of canine renal receptors for the parathyroid hormone-like protein associated with humoral hypercalcemia of malignancy. J Biol Chem. 1989 Apr 15;264(11):6097-103.

    PubMed 2539369
  • Orloff JJ, Ribaudo AE, McKee RL, Rosenblatt M, Stewart AF. A pharmacological comparison of parathyroid hormone receptors in human bone and kidney. Endocrinology. 1992 Oct;131(4):1603-11. doi: 10.1210/endo.131.4.1327716.

    PubMed 1327716
  • Orloff JJ, Reddy D, de Papp AE, Yang KH, Soifer NE, Stewart AF. Parathyroid hormone-related protein as a prohormone: posttranslational processing and receptor interactions. Endocr Rev. 1994 Feb;15(1):40-60. doi: 10.1210/edrv-15-1-40.

    PubMed 8156938
  • Samuels MH, Veldhuis J, Cawley C, Urban RJ, Luther M, Bauer R, Mundy G. Pulsatile secretion of parathyroid hormone in normal young subjects: assessment by deconvolution analysis. J Clin Endocrinol Metab. 1993 Aug;77(2):399-403. doi: 10.1210/jcem.77.2.8345044.

    PubMed 8345044
  • Prank K, Nowlan SJ, Harms HM, Kloppstech M, Brabant G, Hesch RD, Sejnowski TJ. Time series prediction of plasma hormone concentration. Evidence for differences in predictability of parathyroid hormone secretion between osteoporotic patients and normal controls. J Clin Invest. 1995 Jun;95(6):2910-9. doi: 10.1172/JCI117998.

    PubMed 7769133
  • Schmitt CP, Obry J, Feneberg R, Veldhuis JD, Mehls O, Ritz E, Schaefer F. Beta1-adrenergic blockade augments pulsatile PTH secretion in humans. J Am Soc Nephrol. 2003 Dec;14(12):3245-50. doi: 10.1097/01.asn.0000101240.47747.7f.

    PubMed 14638923
  • Chapotot F, Gronfier C, Spiegel K, Luthringer R, Brandenberger G. Relationships between intact parathyroid hormone 24-hour profiles, sleep-wake cycle, and sleep electroencephalographic activity in man. J Clin Endocrinol Metab. 1996 Oct;81(10):3759-65. doi: 10.1210/jcem.81.10.8855835.

    PubMed 8855835
  • Harms HM, Schlinke E, Neubauer O, Kayser C, Wustermann PR, Horn R, Kulpmann WR, von zur Muhlen A, Hesch RD. Pulse amplitude and frequency modulation of parathyroid hormone in primary hyperparathyroidism. J Clin Endocrinol Metab. 1994 Jan;78(1):53-7. doi: 10.1210/jcem.78.1.8288713.

    PubMed 8288713
  • Ledger GA, Burritt MF, Kao PC, O'Fallon WM, Riggs BL, Khosla S. Role of parathyroid hormone in mediating nocturnal and age-related increases in bone resorption. J Clin Endocrinol Metab. 1995 Nov;80(11):3304-10. doi: 10.1210/jcem.80.11.7593443.

    PubMed 7593443
  • el-Hajj Fuleihan G, Klerman EB, Brown EN, Choe Y, Brown EM, Czeisler CA; New Collective Author. The parathyroid hormone circadian rhythm is truly endogenous--a general clinical research center study. J Clin Endocrinol Metab. 1997 Jan;82(1):281-6. doi: 10.1210/jcem.82.1.3683.

    PubMed 8989274
  • Plawner LL, Philbrick WM, Burtis WJ, Broadus AE, Stewart AF. Cell type-specific secretion of parathyroid hormone-related protein via the regulated versus the constitutive secretory pathway. J Biol Chem. 1995 Jun 9;270(23):14078-84. doi: 10.1074/jbc.270.23.14078.

    PubMed 7775469
  • Horwitz 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 12679445
  • Syed MA, Horwitz MJ, Tedesco MB, Garcia-Ocana A, Wisniewski SR, Stewart AF. Parathyroid hormone-related protein-(1--36) stimulates renal tubular calcium reabsorption in normal human volunteers: implications for the pathogenesis of humoral hypercalcemia of malignancy. J Clin Endocrinol Metab. 2001 Apr;86(4):1525-31. doi: 10.1210/jcem.86.4.7406.

    PubMed 11297578
  • Everhart-Caye M, Inzucchi SE, Guinness-Henry J, Mitnick MA, Stewart AF. Parathyroid hormone (PTH)-related protein(1-36) is equipotent to PTH(1-34) in humans. J Clin Endocrinol Metab. 1996 Jan;81(1):199-208. doi: 10.1210/jcem.81.1.8550752.

    PubMed 8550752

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing PTHrP (1-36) in people with Osteoporosis and Humoral 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 11 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: finished, as of the sponsor's last update on 11 Feb 2016. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Dose Limiting Toxicity (DLT) (time frame: 12 hours after the infusion was started then q 8 hours for 7 days). The study lists 4 primary outcomes in all. 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 NCT00580788, which also lists 27 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 11 Feb 2016.

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