Stem Cell Recruitment in Osteoporosis Therapy

NCT01656629 | Terminated Results

• 1 other identifier: NA_00050448
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Osteoporosis is an important health problem in the rapidly-aging demographic. Fragility fractures are devastating consequences of osteoporosis. The most common treatment approach in osteoporosis is inhibition of bone resorption with drugs like alendronate (ALN). Parathyroid hormone (PTH) stimulates bone formation and is the only anabolic drug available. Dual therapy with ALN and PTH is not as effective as single-drug therapy in preventing fracture. Bone progenitor cells (MSCs) are recruited to sites of bone remodeling when a growth factor called Transforming Growth Factor Beta (TGF-β1) is released from bone. Different osteoporosis medicines may have differing effects on this process. The effects of ALN versus PTH on bone progenitor recruitment in humans are unknown. This is a randomized, clinical trial of ALN, PTH, and calcium and vitamin D in post-menopausal women with low bone mass. Women will be treated for 3 months with ALN or PTH or calcium and vitamin D. Data collected will include bone biopsies for histomorphometry and micro computed tomography (µCT), bone marrow aspirates for molecular studies, peripheral blood to detect circulating bone progenitor cells and dual X-ray absorptiometry. The investigators hypothesize that in humans, PTH will 1) increase bone progenitor number, 2) enhance recruitment of bone progenitor cells to bone resorption sites, and 3) increase bone progenitor number in peripheral circulation. Furthermore, the investigators hypothesize that ALN treatment will have the opposite effect. Understanding the differences in bone progenitor cell activity and recruitment during osteoporosis therapy will provide a mechanistic rationale for effective use of PTH and anti-resorptive drugs in osteoporosis treatment.

Conditions

Low Bone Density

Outcome Measures

Primary Outcomes (1)

• The Percent Change in Circulating Osteoprogenitor Cells as Assessed by Flow Cytometry in the Blood Before and After Treatment With Parathyroid Hormone (PTH) or Alendronate (ALN).

  up to 3 months

Secondary Outcomes (2)

• Difference in Bone Formation as Assessed by Bone Histomorphometry on Bone Biopsy Between Treatment Groups

  3 months

• Difference in Osteogenic Potential of Bone Marrow as Measure by Colony Forming Unit Osteoblast (CFU-Ob) Assays Between Treatment Groups

  3 months

Study Arms (3)

teriparatide

ACTIVE COMPARATOR

teriparatide 20 mcg sq for 3 months

Drug: Teriparatide

Alendronate

ACTIVE COMPARATOR

70 mg po weekly for 3 months

Drug: Alendronate

calcium and vitamin D

ACTIVE COMPARATOR

calcium 630 mg vitamin D 500 units daily for 3 months

Dietary Supplement: calcium and vitamin D

Interventions

Teriparatide DRUG

20 mcg subq daily for 3 months

teriparatide

Alendronate DRUG

70 mg weekly for 3 months

Alendronate

calcium and vitamin D DIETARY_SUPPLEMENT

calcium and vitamin D

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Post-menopausal women aged 50-80 years
• T score \< -2.5 at lumbar spine, total hip or femoral neck on dual x-ray absorptiometry (DXA) OR T score \< -1.5 with a personal or family history of fracture

You may not qualify if:

• Previous use of bisphosphonates or Teriparatide; current estrogen therapy; any other osteoporosis therapy in the past 6 months
• Metabolic bone disease other than osteoporosis
• Body mass index (BMI) \< 18
• Weight \> 325 lbs
• Current smoking or current alcohol use that exceeds 3 units of alcohol daily
• Use of medications known to affect bone metabolism
• Renal disease, history of kidney stones or hypercalciuria
• Hypo- or hyperparathyroidism; hypo- or hypercalcemia
• Serum vitamin D level \< 20 ng/dL
• Refusal to adjust their dietary calcium to \<750mg (i.e. two servings per day of calcium rich food)
• History of bone marrow or organ transplant
• History of malignancy or radiation to the bone
• History of esophageal stricture, dysmotility or severe reflux disease
• Gastrointestinal malabsorption
• Use of digoxin

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Bone Diseases, Metabolic

Interventions

Teriparatide; Alendronate; Calcium; Vitamin D

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

There was a high level of variability and this data has not been validated.

Results Point of Contact

• Title: Dr. Suzanne Jan De Beur
• Organization: Johns Hopkins University

sjandebe@jhmi.edu

410-550-0100

Study Officials

• Suzanne Jan De Beur, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2012
• First Posted: August 3, 2012
• Study Start: August 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: August 7, 2020
• Last Updated: August 21, 2020
• Results First Posted: August 8, 2019

Record last verified: 2020-08

Locations

US (1)