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Exercise Training and Thrombotic Risk in Post-menopausal Women (TIME)

Primary Purpose

Thrombosis, Menopause, Exercise Training

Status
Active
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Early and late postmenopausal women
Sponsored by
University of Copenhagen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Thrombosis

Eligibility Criteria

50 Years - 70 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Age: 50-70 years
  • Physical activity ≤ 2 hours per week (except transportation by bike or by walking)
  • BMI ≤ 30

Exclusion Criteria:

  • Age <50 years
  • Injuries that prevent the performance of team sports
  • Participation in other clinical projects
  • Smokes or has smoked within the last 10 years
  • On hormone therapy
  • Not entered menopause
  • Has chronic diseases that are not expected, cf. the groups sought. Including heart problems, atrial fibrillation, cancer, immune diseases and previous strokes with functionally significant sequelae
  • Being treated with oral steroids
  • Has alcohol / drug abuse or is being treated with disulfiram (Antabus)
  • Is unable to understand the contents of the document with informed consent or the experimental procedures

Sites / Locations

  • Ylva Hellsten

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Early postmenopausal women

Late postmenopausal women

Arm Description

Healthy sedentary early postmenopausal women

Healthy sedentary late postmenopausal women

Outcomes

Primary Outcome Measures

Changes in clot microstructure in early and late postmenopausal women after 16 weeks of exercise training
Clot microstructure is measured in a rheometer using unaltered whole blood
Changes in platelet reactivity in early and late postmenopausal women after 16 weeks of exercise training
Platelet reactivity is measured with Light Transmission Aggregometry using platelet rich and platelet poor plasma
Plasma concentration of coagulation factors in early and late postmenopausal women after 16 weeks of exercise training
Coagulation factors II, VII, X, VIII, D-dimer, fibrinogen and thrombin
Changes in vascular function in early and late postmenopausal women after 16 weeks of exercise training
Vascular function is assessed by flow-mediated dilation (FMD) in the brachial artery using ultrasound doppler
Changes in capillary density after 16 weeks of team sports in early and late postmenopausal women
Capillary density will be assessed by histochemistry
Changes in proliferative capacity of endothelial cells after 16 weeks of exercise training in early and late postmenopausal women
From a biopsy sample we isolate endothelial cells and run a proliferation assay
Changes in mitochondrial function of endothelial cells after 16 weeks of exercise training in early and late postmenopausal women
High resolution respirometry
Changes in skeletal muscle protein content important for vascular function after 16 weeks of exercise training in early and late postmenopausal women
Western blots will be used to determine endothelial nitric oxide synthase (eNOS), cyclo-oxygenase 1 and 2, prostacyclin synthase, endothelin receptor A and B, VEGF (vascular endothelial growth factor), Thrombospondin-1, Flk-1 (VEGF receptor). All protein content measures will be presented as arbitrary units.

Secondary Outcome Measures

Changes in blood pressure after 16 weeks of team sports in early and late postmenopausal women
Blood pressure measured at home with an automated blood pressure device. Systolic blood pressure, diastolic blood pressure and mean arterial pressure will be collected.
Changes in maximal oxygen uptake after 16 weeks of team sports in early and late postmenopausal women
Maximal oxygen uptake will be measured using a metabolic cart. The test protocol will be performed on a cycle ergometer using an incremental step test.
Changes in body composition after 16 weeks of team sports in early and late postmenopausal women
Dual-energy x-ray absorptiometry (DXA) will be used to determine fat free mass, fat mass as well as bone mineral content. These values will be presented in absolute (g) as well as relative values (percentage)

Full Information

First Posted
October 8, 2020
Last Updated
May 9, 2023
Sponsor
University of Copenhagen
Collaborators
Swansea University
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1. Study Identification

Unique Protocol Identification Number
NCT04596501
Brief Title
Exercise Training and Thrombotic Risk in Post-menopausal Women
Acronym
TIME
Official Title
Susceptibility to Thrombosis in Post-menopausal Women- Influence of Exercise Training
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
December 1, 2022 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Copenhagen
Collaborators
Swansea University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
At menopausal transition, the risk of cardiovascular diseases increases. This is partly due to aging, but largely also the loss of estrogen, which has many positive effects on the circulation and protects against cardiovascular diseases. It has been suggested that the loss of estrogen may have a negative impact on the otherwise well-documented health promoting effects of exercise training, and that the time after menopause may be crucial for the effect of exercise training on the vascular function, and therefore also for the risk of thrombosis. Literature regarding the effect of exercise training on the risk of thrombosis is limited, and especially in women. The purpose of the present study is to investigate whether the same effects of exercise training in relation to thrombosis is achieved if the exercise is initiated early compared to late after menopause. The aim is to provide knowledge-based recommendations regarding exercise. Teams sports will be used as the training intervention, because team sports benefits physical health and also includes a social element.
Detailed Description
Part of the novelty of this project is to link functional measurements of cardiovascular health at whole body level to cell studies. Cells will be isolated from muscle samples obtained from the post-menopausal women before and after the training intervention. This will enhance the understanding of the changes that occur after prolonged loss of estrogen on thrombotic risk and vascular function, and whether exercise training can alter these parameters.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombosis, Menopause, Exercise Training, Vascular Dilation

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Early postmenopausal women
Arm Type
Experimental
Arm Description
Healthy sedentary early postmenopausal women
Arm Title
Late postmenopausal women
Arm Type
Experimental
Arm Description
Healthy sedentary late postmenopausal women
Intervention Type
Other
Intervention Name(s)
Early and late postmenopausal women
Intervention Description
The intervention involves supervised team sports 1 h 3 x/week for 16 weeks.
Primary Outcome Measure Information:
Title
Changes in clot microstructure in early and late postmenopausal women after 16 weeks of exercise training
Description
Clot microstructure is measured in a rheometer using unaltered whole blood
Time Frame
16 weeks
Title
Changes in platelet reactivity in early and late postmenopausal women after 16 weeks of exercise training
Description
Platelet reactivity is measured with Light Transmission Aggregometry using platelet rich and platelet poor plasma
Time Frame
16 weeks
Title
Plasma concentration of coagulation factors in early and late postmenopausal women after 16 weeks of exercise training
Description
Coagulation factors II, VII, X, VIII, D-dimer, fibrinogen and thrombin
Time Frame
16 weeks
Title
Changes in vascular function in early and late postmenopausal women after 16 weeks of exercise training
Description
Vascular function is assessed by flow-mediated dilation (FMD) in the brachial artery using ultrasound doppler
Time Frame
16 weeks
Title
Changes in capillary density after 16 weeks of team sports in early and late postmenopausal women
Description
Capillary density will be assessed by histochemistry
Time Frame
16 weeks
Title
Changes in proliferative capacity of endothelial cells after 16 weeks of exercise training in early and late postmenopausal women
Description
From a biopsy sample we isolate endothelial cells and run a proliferation assay
Time Frame
16 weeks
Title
Changes in mitochondrial function of endothelial cells after 16 weeks of exercise training in early and late postmenopausal women
Description
High resolution respirometry
Time Frame
16 weeks
Title
Changes in skeletal muscle protein content important for vascular function after 16 weeks of exercise training in early and late postmenopausal women
Description
Western blots will be used to determine endothelial nitric oxide synthase (eNOS), cyclo-oxygenase 1 and 2, prostacyclin synthase, endothelin receptor A and B, VEGF (vascular endothelial growth factor), Thrombospondin-1, Flk-1 (VEGF receptor). All protein content measures will be presented as arbitrary units.
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
Changes in blood pressure after 16 weeks of team sports in early and late postmenopausal women
Description
Blood pressure measured at home with an automated blood pressure device. Systolic blood pressure, diastolic blood pressure and mean arterial pressure will be collected.
Time Frame
16 weeks
Title
Changes in maximal oxygen uptake after 16 weeks of team sports in early and late postmenopausal women
Description
Maximal oxygen uptake will be measured using a metabolic cart. The test protocol will be performed on a cycle ergometer using an incremental step test.
Time Frame
16 weeks
Title
Changes in body composition after 16 weeks of team sports in early and late postmenopausal women
Description
Dual-energy x-ray absorptiometry (DXA) will be used to determine fat free mass, fat mass as well as bone mineral content. These values will be presented in absolute (g) as well as relative values (percentage)
Time Frame
16 Weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age: 50-70 years Physical activity ≤ 2 hours per week (except transportation by bike or by walking) BMI ≤ 30 Exclusion Criteria: Age <50 years Injuries that prevent the performance of team sports Participation in other clinical projects Smokes or has smoked within the last 10 years On hormone therapy Not entered menopause Has chronic diseases that are not expected, cf. the groups sought. Including heart problems, atrial fibrillation, cancer, immune diseases and previous strokes with functionally significant sequelae Being treated with oral steroids Has alcohol / drug abuse or is being treated with disulfiram (Antabus) Is unable to understand the contents of the document with informed consent or the experimental procedures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ylva Hellsten, Dr.Med.Sci.
Organizational Affiliation
Nutrition, Exercise and Sports, 2200 Copenhagen, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ylva Hellsten
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No

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Exercise Training and Thrombotic Risk in Post-menopausal Women

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