Teriparatide (Forsteo) Treatment in Postmenopausal Women: Mechanism of Action

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Sheffield Teaching Hospitals NHS Foundation Trust
Sponsor:
Information provided by:
Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01293292
First received: February 4, 2011
Last updated: December 14, 2012
Last verified: December 2012
  Purpose

Previously the approach to treatment of osteoporosis has been to use medications which prevent excessive resorption of bone. More recently medications that build up new bone, i.e. anabolic treatments, have been, and are being, developed. The investigators would like to develop a strategy for evaluating the effectiveness of anabolic therapies by studying a currently available therapy (teriparatide). This strategy could then be used to assess new anabolic treatments as they are developed for use in humans.

The aims of this study are 1) to fully describe the changes in bone turnover in response to teriparatide by biochemical marker type and by time; 2) to fully describe the changes in bone mineral density (BMD) in response to teriparatide by site, bone compartment and time.

If this study is able to identify an early response to treatment, then this will help speed up drug development in this area, by allowing the identification of promising new anabolic drugs and enabling us to understand their mechanism of action. This will benefit the investigators patients as the investigators will have a better understanding of how these drugs work.


Condition Intervention Phase
Osteoporosis
Drug: Teriparatide
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Teriparatide (Forsteo) Treatment in Postmenopausal Women: Mechanism of Action. A Two-year Open-label Single-arm Study of Teriparatide in Secondary Care

Resource links provided by NLM:


Further study details as provided by Sheffield Teaching Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • Volumetric bone mineral density (BMD) of the lumbar spine (mg hydroxyapatite/cm3) [ Time Frame: 0 to 104 weeks ] [ Designated as safety issue: No ]
    Change in volumetric BMD of the lumbar spine (vertebrae L1-3) (mg hydroxyapatite/cm3) measured by quantitative computed tomography (QCT) from 0 to 104 weeks treatment.


Secondary Outcome Measures:
  • Lumbar spine, total hip and whole body bone mineral density (g/cm2) [ Time Frame: 0 to 104 weeks ] [ Designated as safety issue: No ]
    Changes in lumbar spine, total hip and whole body bone mineral density (g/cm2) measured by dual x-ray absorptiometry (DXA) from 0 to 104 weeks.

  • Biochemical markers of bone turnover [ Time Frame: 0 to 104 weeks ] [ Designated as safety issue: No ]
    Changes in biochemcial markers of bone turnover (OC, PINP, bone ALP, urinary NTX, serum CTX, sclerostin, DKK-1) from 0 to 104 weeks.

  • Distal tibia and radius volumetric body bone mineral density (BMD) (mg hydroxyapatite/cm3) [ Time Frame: 0 to 104 weeks ] [ Designated as safety issue: No ]
    Changes in distal tibia and radius volumetric bone mineral density (mg hydroxyapatite/cm3) measured by High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) from 0 to 104 weeks.


Estimated Enrollment: 20
Study Start Date: January 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Teriparatide
    Teriparatide (Forsteo) 20 mcg subcutaneous injection once daily. Duration 104 weeks.
    Other Name: Forsteo
  Eligibility

Ages Eligible for Study:   up to 84 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Subjects must:

  • Have a bone mineral density T-score (at the lumbar spine or total hip) of less than or equal to -2.5
  • Be female
  • Be at least 5 years post menopausal (more than 5 years since their last menstrual period) but <85 years old.
  • Be ambulatory
  • Be able and willing to participate in the study and provide written informed consent
  • Have a serum 25(OH)2 vitamin D3 >50 nmol/L (after vitamin D3 loading)

Exclusion Criteria

Patients will not be admitted to the study if they exhibit any of the following:

  • Evidence of a clinically significant organic disease which could prevent the patient from completing the study
  • A body mass index less than 18 or greater than 35
  • Abuse of alcohol or use illicit drugs (information obtained from medical history) or who consumed more than 4 servings of any alcoholic beverage one day prior to the visit (i.e., subjects who might be binge drinkers)
  • Any history of cancer within the past 5 years excluding skin cancer non melanomas
  • Any history of ongoing conditions or diseases known to cause abnormalities of calcium metabolism or skeletal health including Paget's disease of bone
  • Chronic renal disease (as defined by an estimated glomerular filtration rate of ≤ 30mL/min)
  • Acute or chronic hepatic disease
  • Malabsorption syndromes
  • Hyperthyroidism as manifested by TSH outside the lower limit of the normal range
  • Hyperparathyroidism
  • Hypocalcemia or hypercalcemia
  • Osteomalacia
  • Cushing's syndrome
  • Current use of glucocorticoid therapy
  • A corrected serum calcium less than 2.2 mmol/L and a PTH above 100 ng/L (that persists after testing and treatment for vitamin D deficiency)
  • A history of any known condition that would interfere with the assessment of DXA at either lumbar spine or femoral neck
  • Markedly abnormal clinical laboratory parameters that are assessed as clinically significant by the investigator
  • Any previous use of bisphosphonate
  • Use any of the following medications within 12 months of starting study drug
  • Any fluoride with the exception of use for oral hygiene
  • Strontium Ranelate
  • Other bone agents (e.g. SERM, isoflavones, HRT)
  • Participation in another clinical trial involving active therapy 3 months prior to enrolment
  • Less than 5 years since menopause
  • Bilateral fractures in the measurement regions (hip, tibia and forearm)
  • Recent fracture within the last 12 months
  • Prior radiation therapy which may involve the skeleton
  • Hypersensitivity to teriparatide or any of its excipients
  • Unexplained elevations of alkaline phosphatase
  • Any known contraindication to the use of teriparatide
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01293292

Contacts
Contact: Katharine Knight, PhD +44 114 2266401 katharine.knight@sth.nhs.uk

Locations
United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust Recruiting
Sheffield, South Yorkshire, United Kingdom, S5 7AU
Principal Investigator: Richard Eastell, MD, FRCP, FRCPath, FMedSci         
Sponsors and Collaborators
Sheffield Teaching Hospitals NHS Foundation Trust
Investigators
Study Director: Richard Eastell, MD, FRCP, FRCPath, FMedSci University of Sheffield
Principal Investigator: Jennifer Walsh, PhD MRCP Sheffield Teaching Hospitals NHS Foundation Trust
Principal Investigator: Eugene McCloskey, MD, FRCPI University of Sheffield
Principal Investigator: Nicola Peel, DM FRCP Sheffield Teaching Hospitals NHS Foundation Trust
Principal Investigator: Angela Rogers, BSc (Hons), PhD, MCSP University of Sheffield
Principal Investigator: Margaret Paggiosi, Bsc (Hons), PhD, MICR Sheffield Teaching Hospitals NHS Foundation Trust
Principal Investigator: Lang Yang, PhD CSci University of Sheffield
Principal Investigator: David Hughes, BMedSci MBChB PhD FRCPath Sheffield Teaching Hospitals NHS Foundation Trust
Principal Investigator: Mark Wilkinson, PhD, FRCS (Tr&Orth) University of Sheffield
  More Information

No publications provided

Responsible Party: Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01293292     History of Changes
Other Study ID Numbers: STH15466, 2010-021009-19
Study First Received: February 4, 2011
Last Updated: December 14, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Sheffield Teaching Hospitals NHS Foundation Trust:
Osteoporosis
Forsteo
Teriparatide

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Teriparatide
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014