3-Week Parathyroid Hormone-related Protein (PTHrP) Dose Escalation Study in Post-Menopausal Women

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

61 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-07-31

Study Completion Date

2008-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The main purpose of this study is to determine the safety and effectiveness of three week daily subcutaneous injections of Parathyroid Hormone-related Protein (1-36). Previous studies indicated that PTHrP has a skeletal 'anabolic' or bone-building effect, and has shown to increase bone mineral density in postmenopausal women with osteoporosis. Safety of PTHrP will be determined by measurements of blood pressure and pulse, serum blood calcium levels and subjective symptoms. Effectiveness will be measured by changes in measurements of blood and urine markers of bone turnover.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Comparison Study of PTHrP and PTH to Treat Osteoporosis

NCT00853723

Osteoporosis

COMPLETED PHASE2

One Week Comparison Study of PTH and PTHrP Infusions

NCT01333267

Osteoporosis Hypercalcemia of Malignancy Hyperparathyroidism +1 more

WITHDRAWN PHASE1

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

NCT00580788

Osteoporosis Humoral Hypercalcemia of Malignancy Hyperparathyroidism

COMPLETED EARLY_PHASE1

7 Day Continuous Parathyroid Hormone IV Infusion

NCT00377312

Osteoporosis Bone Diseases, Endocrine Hyperparathyroidism

COMPLETED EARLY_PHASE1

"PTHrP(1-36) IV Dose Escalation Study"

NCT00177411

Osteoporosis

WITHDRAWN PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Parathyroid Hormone-related Protein (1-36) or PTHrP is a neuroendocrine peptide which shares significant homology with the only currently FDA approved anabolic agent for the treatment of osteoporosis: parathyroid hormone(1-34) or PTH. PTH, when given alone, has shown to increase lumbar spine bone mass by 12-15% over a 2-3 year period.

Previous studies indicate PTHrP may have a pure anabolic effect on bone. Postmenopausal women taking estrogen with osteoporosis who received daily subcutaneous PTHrP for 3 months exhibited a 4.7% increase in bone mineral density compared to those taking placebo. There were no side effects associated with PTHrP, despite the fact that the doses given were 20 times the usual doses of PTH. In another study, young healthy volunteers received a single, one-time subcutaneous doses of PTHrP in amounts up to 2 mg without any dose limiting toxicities.

This study will directly compare the effect of placebo and escalating doses of PTHrP given subcutaneously to postmenopausal women for three weeks. Each subject will have four outpatient visits and one inpatient 24-hour visit on the last day. 20 women in phase I will receive either placebo or 500 micrograms/day of PTHrP. 500 micrograms/day was selected as the lowest dose because it is similar to the dose used in our previous 3 month placebo controlled study. In Phase II, the doses of PTHrP will be increased in increments of approximately 30% for each successive group, i.e., 750, 1000, 1250, and 1500 micrograms. After the first group of 10 successfully receives 500 micrograms/day for 21 days, increased doses will be given to groups of three subjects until evidence of dose limiting toxicity (DLT) occurs, or a maximum dose of 1,500 micrograms is reached. Dose limiting toxicities are specified in the protocol and comprise either one major criteria: hypotension, orthostatic hypotension, tachycardia, hypertension, hypercalcemia or hypophosphatemia; or two minor criteria: flushing, nausea/vomiting, abdominal or muscle cramps, dizziness/lightheadedness, palpitations, or any other unpleasant subjective symptom.

If a particular dose of PTHrP causes a dose-limiting toxicity, the immediately preceding lower dose will be defined as the maximum safely tolerated dose. Once the maximum safely tolerated dose is determined, it will be given to a total of ten healthy subjects to ensure that is is safe and well tolerated.

Study methods include outpatient visits on days 1, 5, 10, 15, and an in-patient visit on day 21 for lab collection and patient examination. Blood and urine safety labs consist of serum ionized calcium, total calcium, creatinine, phosphorus and albumin. Efficacy labs consist of urine and blood measurements of 25-hydroxy vitamin D, 1,25 vitamin D, PTH, osteocalcin, bone specific alkaline phosphatase, procollagen peptide-1, C-telopeptide (CTx), N-telopeptide (NTx), Insulin-like growth factors (IgF) and serum free deoxypyridinoline (DPD).

Subject population includes up to 48 healthy 50-75 year old postmenopausal women who are Caucasian, Asian, and Hispanic. African-Americans are excluded from the study since it is well documented that African-Americans have clear quantitative differences in bone density and sensitivity to parathyroid hormone. No bone densitometry scans are done during this study.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Osteoporosis Osteoporosis, Postmenopausal

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1 - PTHrP Group

Group receiving study drug: PTHrP(1-36)

Group Type ACTIVE_COMPARATOR

Parathyroid Hormone-related Protein

Intervention Type DRUG

PTHrP(1-36) starting at 500 micrograms, then increasing by 125 micrograms up to a maximum of 1,500 micrograms.

2 - Single Blind Placebo Group

Receives placebo injections daily via subcutaneous injection

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo drug via subcutaneous injection in single blinded fashion daily for 3 weeks

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Parathyroid Hormone-related Protein

PTHrP(1-36) starting at 500 micrograms, then increasing by 125 micrograms up to a maximum of 1,500 micrograms.

Intervention Type DRUG

Placebo

Placebo drug via subcutaneous injection in single blinded fashion daily for 3 weeks

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

study drug Placebo group

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Women
* Caucasian
* Hispanic
* Asian
* One year past onset of menopause
* Weigh between 50 and 90 kilograms

Exclusion Criteria

* Taking bisphosphonates in the last 2 years
* Estrogen replacement hormones in last year
* SERMS in last year
* One weeks worth of PTHrP, PTH or an analog of PTH in past year
* Recent non-traumatic bone fracture within last year
* Significant uncontrolled cardiac, vascular, renal, pulmonary, endocrine or rheumatologic disease
* History of malignancy
* Anemia
* Significant alcohol or drug abuse
* Receiving any investigational drug within past 90 days
* Medications that interfere with metabolism or renal clearance of study drug, oral or systemic glucocorticoids of \> 5 mg/day prednisone (or equivalent) over the past year
* Thiazide-type diuretics
* Abnormal screening labs (calcium, vit D and PTH, CBC)

Minimum Eligible Age

50 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes