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NCT00580788 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
EARLY PHASE1
Status at capture
COMPLETED
Registry last update
2016-02-11

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Dose Limiting Toxicity (DLT)

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outcome · POSTED

1,25 Vitamin D

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outcome · POSTED

24 Hour Urine Calcium

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outcome · POSTED

Tubular Maximum of Phosphorous (TmP/GFR)

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outcome · POSTED

Total Serum Calcium

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outcome · POSTED

Ionized Serum Calcium

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outcome · POSTED

Serum Phosphorous

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Amino-terminal Peptides of Procollagen 1 (P1NP)

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outcome · POSTED

Bone Specific Alkaline Phosphatase (BSAP)

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outcome · POSTED

Parathyroid Hormone (1-84)

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outcome · POSTED

Fractional Excretion of Calcium

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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 * 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
healthy Volunteers
true
maximum Age
35 Years
minimum Age
24 Years
sex
ALL
std Ages
  1. ADULT
Treatment arms and interventions
arm Groups
  1. description
    PTHrP(1-36) at 2 picomoles/kg/hr for one week.
    intervention Names
    1. Drug: PTHrP (1-36)
    label
    PTHrP(1-36) 2 pmol/kg/hr
    type
    EXPERIMENTAL
  2. description
    PTHrP(1-36) at 4 picomoles/kg/hr for one week.
    intervention Names
    1. Drug: PTHrP (1-36)
    label
    PTHrP (1-36) 4 pmol/kg/hr
    type
    EXPERIMENTAL
  3. description
    PTHrP(1-36) at 5 picomoles/kg/hr for one week.
    intervention Names
    1. Drug: PTHrP (1-36)
    label
    PTHrP(1-36) 5 pmol/kg/hr
    type
    EXPERIMENTAL
  4. description
    PTHrP(1-36) at 6 picomoles/kg/hr for one week.
    intervention Names
    1. Drug: PTHrP (1-36)
    label
    PTHrP(1-36) 6 pmol/kg/hr
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. PTHrP (1-36) 4 pmol/kg/hr
    2. PTHrP(1-36) 2 pmol/kg/hr
    3. PTHrP(1-36) 5 pmol/kg/hr
    4. PTHrP(1-36) 6 pmol/kg/hr
    description
    IND # 49,175
    name
    PTHrP (1-36)
    other Names
    1. Parathyroid Hormone-related Protein (1-36)
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
SINGLE_GROUP
masking Info
masking
SINGLE
who Masked
  1. PARTICIPANT
Enrollment
count
14
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Dose Limiting Toxicity (DLT)
    time Frame
    12 hours after the infusion was started then q 8 hours for 7 days
  2. description
    mg/dl
    measure
    Total Serum Calcium
    time Frame
    12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
  3. description
    mg/dl
    measure
    Ionized Serum Calcium
    time Frame
    12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
  4. description
    mg/dl
    measure
    Serum Phosphorous
    time Frame
    12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
secondary Outcomes
  1. description
    pg/ml
    measure
    1,25 Vitamin D
    time Frame
    Baseline and Daily through day 8 then at follow-up visit
  2. description
    mg/gm creatinine collected on day 7 of PTHrP infusion
    measure
    24 Hour Urine Calcium
    time Frame
    24 hours
  3. description
    mg/dl calculated from daily second morning void
    measure
    Tubular Maximum of Phosphorous (TmP/GFR)
    time Frame
    daily
  4. description
    % change from baseline
    measure
    Serum Amino-terminal Telopeptide of Collagen -1 (sNTX)
    time Frame
    Baseline, Daily, and 1 week follow-up
  5. description
    % change from baseline
    measure
    Serum Carboxy-terminal Telopeptide of Collagen -1 (sCTX)
    time Frame
    Baseline, Daily, and 1 week follow-up
  6. description
    % change from baseline
    measure
    Amino-terminal Peptides of Procollagen 1 (P1NP)
    time Frame
    Baseline, Daily, and 1 week follow-up
  7. description
    % change from baseline
    measure
    Bone Specific Alkaline Phosphatase (BSAP)
    time Frame
    Baseline, Daily, and 1 week follow-up
  8. description
    pg/ml
    measure
    Parathyroid Hormone (1-84)
    time Frame
    Baseline and Daily
  9. description
    % calculated from daily second morning void
    measure
    Fractional Excretion of Calcium
    time Frame
    daily
Full study description
brief 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 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.
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.
Source references
references
  1. citation
    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.
    pmid
    1658941
    type
    BACKGROUND
  2. citation
    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.
    pmid
    2539369
    type
    BACKGROUND
  3. citation
    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.
    pmid
    1327716
    type
    BACKGROUND
  4. citation
    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.
    pmid
    8156938
    type
    BACKGROUND
  5. citation
    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.
    pmid
    8345044
    type
    BACKGROUND
  6. citation
    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.
    pmid
    7769133
    type
    BACKGROUND
  7. citation
    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.
    pmid
    14638923
    type
    BACKGROUND
  8. citation
    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.
    pmid
    8855835
    type
    BACKGROUND
  9. citation
    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.
    pmid
    8288713
    type
    BACKGROUND
  10. citation
    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.
    pmid
    7593443
    type
    BACKGROUND
  11. citation
    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.
    pmid
    8989274
    type
    BACKGROUND
  12. citation
    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.
    pmid
    7775469
    type
    BACKGROUND
Source notices and limitations
    Discovery and provenance
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      query cond
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      query disease state id
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    Preserved source evidence · Not medical advice