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Effects of Acute Estrogen Therapy on Bone Formation

Primary Purpose

Bone Loss, Age-related

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Estrogens (Climara)

About this trial

This is an interventional basic science trial for Bone Loss, Age-related focused on measuring estrogen, aging

Eligibility Criteria

65 Years - undefined (Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

At least 10 years postmenopausal; Menopause is defined as no menses for at least 1 year (or documented ovariectomy) and a serum follicle-stimulating hormone (FSH) above 30 IU/L.

Exclusion Criteria:

Clinically significant abnormality in any of the following screening laboratory studies (to be reviewed and determined by PI or CI) : serum 25-hydroxyvitamin D (see below); phosphorus (minor change outside of normal guidelines is acceptable and does not impact the study); alkaline phosphatase and aspartate transaminase (AST) (minor change outside of normal guidelines is acceptable but not to exceed 50% above normal or ineligible); Creatinine (Cr) (minor change outside of normal guidelines is acceptable but not to exceed a value of 1.2 or ineligible); serum calcium must not exceed upper limits of normal guidelines or subject ineligible; FSH needs to be ≥30; thyroid-stimulating hormone (TSH) needs to be above 0.3 and not > 10;
Presence of significant liver disease, renal disease, malignancy (including breast cancer and myeloma), malabsorption syndrome, hypoparathyroidism, hyperparathyroidism, acromegaly, Cushing's syndrome, hypopituitarism, severe chronic obstructive pulmonary disease, untreated gallbladder disease, history of myocardial infarction (MI) or stroke, or history of thrombophlebitis or deep venous thrombosis;
Undergoing treatment with any of the following drugs: adrenocorticoid steroids (3 months or longer at anytime or > 10 days of treatment within the previous 12 months), anticonvulsant therapy (within the previous year), sodium fluoride (any history of treatment with fluoride), pharmacological doses of thyroid hormone (causing decline of TSH below normal), calcium supplementation of more than 1200 mg/d (within the preceding 3 months), bisphosphonates in the past, calcitonin (within the past six months), E therapy or treatment with a selective estrogen receptor modulator (within the past 6 months), parathyroid hormone (PTH) use in the past. Subjects with a clinical history of an osteoporotic fracture (vertebral, hip, or distal forearm) within the previous 3 years will also be excluded.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Estrogens

Arm Description

Estrogens treatment: Intervention with short course (3 weeks) of treatment with transdermal estrogen (0.1mg/d)

Outcomes

Primary Outcome Measures

Gene expression (RNAseq analysis of gene expression from needle bone biopsies)

RNAseq analysis of gene expression from needle bone biopsies

Secondary Outcome Measures

Full Information

NCT ID

NCT02349113

First Posted

January 23, 2015

Last Updated

February 13, 2015

Sponsor

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT02349113

Brief Title

Effects of Acute Estrogen Therapy on Bone Formation

Official Title

Effects of Acute Estrogen Therapy on Bone Formation

Study Type

Interventional

2. Study Status

Record Verification Date

February 2015

Overall Recruitment Status

Completed

Study Start Date

February 2012 (undefined)

Primary Completion Date

September 2012 (Actual)

Study Completion Date

September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study is being done to study age-related bone changes in women. The investigators know that the major cause of osteoporosis is a shortage of the female hormone estrogen. This study will look closer at how this shortage of estrogen works to cause a decrease in bone formation.

Detailed Description

Estrogen (E) deficiency is the major cause of postmenopausal osteoporosis. Understanding the mechanisms by which E regulates bone metabolism is critical for developing novel approaches to prevent and treat this disorder. We will focus on defining mechanisms for the age-related decrease in bone formation and the role of E deficiency in mediating this decrease. We will use novel methods we have developed to examine gene expression in highly purified bone marrow osteoblastic cells. We will test whether the increase in bone formation previously observed following acute E treatment in women is associated with an increase in markers of Wnt/bone morphogenetic protein (BMP) signaling and/or production and in othe genes related to bone formation by osteoblastic cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bone Loss, Age-related

Keywords

estrogen, aging

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Estrogens

Arm Type

Experimental

Arm Description

Estrogens treatment: Intervention with short course (3 weeks) of treatment with transdermal estrogen (0.1mg/d)

Intervention Type

Drug

Intervention Name(s)

Estrogens (Climara)

Other Intervention Name(s)

Climara

Intervention Description

Treatment with estrogens: Estradiol dermal patch 0.1mg/d transdermally

Primary Outcome Measure Information:

Title

Gene expression (RNAseq analysis of gene expression from needle bone biopsies)

Description

RNAseq analysis of gene expression from needle bone biopsies

Time Frame

3 weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: At least 10 years postmenopausal; Menopause is defined as no menses for at least 1 year (or documented ovariectomy) and a serum follicle-stimulating hormone (FSH) above 30 IU/L. Exclusion Criteria: Clinically significant abnormality in any of the following screening laboratory studies (to be reviewed and determined by PI or CI) : serum 25-hydroxyvitamin D (see below); phosphorus (minor change outside of normal guidelines is acceptable and does not impact the study); alkaline phosphatase and aspartate transaminase (AST) (minor change outside of normal guidelines is acceptable but not to exceed 50% above normal or ineligible); Creatinine (Cr) (minor change outside of normal guidelines is acceptable but not to exceed a value of 1.2 or ineligible); serum calcium must not exceed upper limits of normal guidelines or subject ineligible; FSH needs to be ≥30; thyroid-stimulating hormone (TSH) needs to be above 0.3 and not > 10; Presence of significant liver disease, renal disease, malignancy (including breast cancer and myeloma), malabsorption syndrome, hypoparathyroidism, hyperparathyroidism, acromegaly, Cushing's syndrome, hypopituitarism, severe chronic obstructive pulmonary disease, untreated gallbladder disease, history of myocardial infarction (MI) or stroke, or history of thrombophlebitis or deep venous thrombosis; Undergoing treatment with any of the following drugs: adrenocorticoid steroids (3 months or longer at anytime or > 10 days of treatment within the previous 12 months), anticonvulsant therapy (within the previous year), sodium fluoride (any history of treatment with fluoride), pharmacological doses of thyroid hormone (causing decline of TSH below normal), calcium supplementation of more than 1200 mg/d (within the preceding 3 months), bisphosphonates in the past, calcitonin (within the past six months), E therapy or treatment with a selective estrogen receptor modulator (within the past 6 months), parathyroid hormone (PTH) use in the past. Subjects with a clinical history of an osteoporotic fracture (vertebral, hip, or distal forearm) within the previous 3 years will also be excluded.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sundeep Khosla, MD

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

12. IPD Sharing Statement

Citations:

PubMed Identifier

26402159

Citation

Farr JN, Roforth MM, Fujita K, Nicks KM, Cunningham JM, Atkinson EJ, Therneau TM, McCready LK, Peterson JM, Drake MT, Monroe DG, Khosla S. Effects of Age and Estrogen on Skeletal Gene Expression in Humans as Assessed by RNA Sequencing. PLoS One. 2015 Sep 24;10(9):e0138347. doi: 10.1371/journal.pone.0138347. eCollection 2015.

Results Reference

derived

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Effects of Acute Estrogen Therapy on Bone Formation

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