Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

DHEA Augmentation of Musculoskeletal Adaptations to Exercise in Older Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03227458
Recruitment Status : Recruiting
First Posted : July 24, 2017
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
To determine whether the musculoskeletal adaptations to bone-loading exercise can be significantly augmented in older women (aged 60-85) with low bone mass (osteopenia; T-scores <-1.0 and >-2.5) by restoring serum DHEAS to young adult levels by oral DHEA replacement.

Condition or disease Intervention/treatment Phase
Low Bone Mass Other: DHEA Other: Placebo Behavioral: Exercise Not Applicable

Detailed Description:
This will be the first study to measure changes in areal bone mineral density (aBMD) and fat-free mass (FFM) in response to dehydroepiandrosterone (DHEA) alone and combined with exercise in postmenopausal women. The body of evidence from carefully executed Randomized Controlled Studies (RCTs) provides support for DHEA therapy to increase aBMD and FFM in older women. Less is known about whether DHEA therapy enhances the effects of exercise on the aging musculoskeletal system when an appropriate mechanical stimulus is applied.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: All participants will take 1 study pill (50 mg DHEA or placebo: double-blinded) daily for 36 weeks. The research pharmacist will dispense study drug according to the randomization code and maintain drug dispensation records, which will be monitored by the study biostatistician. Two-thirds of participants will engage in bone-loading exercise 3 days per week for the 36 weeks.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Study drug will be masked. 50 mg DHEA or placebo: double-blinded. Exercise will not be masked.
Primary Purpose: Prevention
Official Title: DHEA Augmentation of Musculoskeletal Adaptations to Exercise in Older Women
Actual Study Start Date : January 31, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Exercise and DHEA
1 study pill containing 50 mg of DHEA daily for 36 weeks and supervised bone-loading exercise on 3 days per week for 36 weeks.
Other: DHEA
Participants will take 1 study pill (50 mg DHEA) daily for 36 weeks.
Other Name: DHEA therapy

Behavioral: Exercise
bone-loading exercise on 3 days per week for 38 weeks
Other Name: bone-loading exercise

Active Comparator: Exercise and Placebo
1 study pill containing placebo daily for 36 weeks and supervised bone-loading exercise on 3 days per week for 36 weeks.
Other: Placebo
Participants will take placebo daily for 36 weeks.

Behavioral: Exercise
bone-loading exercise on 3 days per week for 38 weeks
Other Name: bone-loading exercise

Active Comparator: DHEA only
1 study pill containing 50 mg of DHEA daily for 36 weeks
Other: DHEA
Participants will take 1 study pill (50 mg DHEA) daily for 36 weeks.
Other Name: DHEA therapy




Primary Outcome Measures :
  1. Change in lumbar spine aBMD [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in lumbar spine aBMD


Secondary Outcome Measures :
  1. Change in total hip aBMD [ Time Frame: 36 Weeks ]
    mean change from baseline in total hip aBMD

  2. Change in regional hip aBMD [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in regional hip aBMD

  3. Change in Vertebral (L1-2) total vBMD [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in vertebral total volumetric BMD

  4. Change in Vertebral (L1-2) cortical vBMD [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in vertebral cortical volumetric BMD

  5. Change in Vertebral (L1-2) trabecular vBMD [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in vertebral trabecular volumetric BMD

  6. Change in Femoral total vBMD [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in femoral total volumetric BMD

  7. Change in Femoral cortical vBMD [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in femoral cortical volumetric BMD

  8. Change in Femoral trabecular vBMD [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in femoral trabecular volumetric BMD

  9. Change in Vertebral (L1-2) strength, stance model [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in the estimated strength of L1-2 vertebrae in a stance model

  10. Change in Vertebral (L1-2) strength, fall model [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in the estimated strength of L1-2 vertebrae in a fall model

  11. Change in Proximal femur strength, stance model [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in the estimated strength of the proximal femur in a stance model

  12. Change in Proximal femur strength, fall model [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in the estimated strength of the proximal femur in a fall model

  13. Change in Total body fat-free mass [ Time Frame: Baseline and 36 Weeks ]
    mean change from baseline in total body fat-free mass



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   60 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • non-frail, as determined by short physical performance battery (SPPB) score > 9 (0-12 scale);
  • 5 years or longer since menopause (defined as last menstrual period);
  • willing to participate in a 36-week exercise program that will start at a moderate intensity and gradually progress to a higher intensity;
  • willing to be randomized to an exercise or a no-exercise arm of the study;
  • willing to take DHEA (50mg/d) or a placebo pill daily and remain blinded for up to 36 weeks;
  • not performing resistance exercise training or high impact weight-bearing exercise (e.g., jogging) ≥ 2 days per week in the past 6 months;
  • ambulatory without assistive devices;
  • serum DHEAS < 140 μg/dL (3.8 μmol/L);
  • low bone mass defined as lumbar spine or proximal hip aBMD t-scores < -1.0 and > -2.5;
  • evidence of a negative (no findings suspicious for breast cancer) mammogram within the past 12 months;
  • planning to reside in the Denver area for the duration of the study.

Exclusion Criteria:

  • uncontrolled hypertension defined as resting sBP >150 mmHg or dBP >90 mmHg; participants who do not meet these criteria at first screening will be re-evaluated, including follow-up evaluation by their Primary Care Physician (PCP) with initiation or adjustment of anti-hypertensive medications;
  • diagnosed ischemic heart disease or indicators of unstable ischemic heart disease (e.g., angina, ST segment depression) or arrhythmias at rest or during the Gated Exercise Test (GXT) without negative follow-up evaluation will be cause for exclusion; follow-up evaluation must include diagnostic testing (e.g., thallium stress test) with interpretation by a cardiologist;
  • diagnosis of heart failure, clinically significant aortic stenosis, uncontrolled angina, or uncontrolled arrhythmia.
  • pulmonary disease requiring use of oral steroids within the previous 6 months or the use of supplemental oxygen ≥ 4L with physical exertion
  • orthopedic problems (e.g., severe osteoarthritis, rheumatoid arthritis) that greatly limit the ability to perform moderate to high intensity resistance exercise (e.g., unable to be properly positioned in exercise equipment or to have severely restricted range of motion even after modifications have been made)
  • hip fracture, hip or knee replacement, or spinal surgery in the past 6 months;
  • undergoing physical therapy involving the lower extremities;
  • HCT > 54%;
  • thyroid dysfunction, defined as an ultrasensitive thyroid stimulating hormone (TSH) < 0.5 or > 5.0 μU/mL; volunteers with abnormal TSH values will be re-considered for participation in the study after follow-up evaluation by their PCP with initiation or adjustment of thyroid hormone replacement;
  • acute liver disease indicated by liver function tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase) ≥ 1.5X upper limits of normal;
  • estimated glomerular filtration rate (eGFR) < 45, using MDRD equation (Levey et al, Annals Inter Med, 1999; Munter et al, Clin J Am Soc Nephol, 2009);
  • poorly controlled diabetes mellitus based on HbA1c > 8.5%, or use of insulin;
  • fasted serum triglycerides > 400 mg/dL;
  • serum 25-OH vitamin D <20 ng/mL; volunteers will be re-considered for participation in the study after follow-up evaluation by their PCP with initiation or adjustment of vitamin D supplementation;
  • use of DHEA supplementation or sex hormones in the past 6 months;
  • use in the past 6 months of any medications known to alter bone metabolism (e.g., oral glucocorticoids, bone anti-resorptive agents);
  • documented history of cognitive impairment or dementia, or Mini-Cog < 4;
  • current smoker;
  • personal history of breast, ovarian, metastatic endometrial, or cervical cancer;
  • any cancer requiring treatment in the past 3 years except non-melanoma skin cancers;
  • un-diagnosed vaginal bleeding;
  • women who, in the judgment of the study physician, appear incapable of safely participating in the exercise (e.g., neuromuscular/musculoskeletal impairment).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03227458


Contacts
Layout table for location contacts
Contact: Catherine Jankowski, PhD 303-724-7383 catherine.jankowski@ucdenver.edu

Locations
Layout table for location information
United States, Colorado
University of Colorado Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Catherine Jankowski, PhD    303-724-7383    catherine.jankowski@ucdenver.edu   
Principal Investigator: Catherine Jankowski, PhD         
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Layout table for investigator information
Principal Investigator: Catherine Jankowski, PhD University of Colorado, Denver

Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03227458     History of Changes
Other Study ID Numbers: 16-2427
First Posted: July 24, 2017    Key Record Dates
Last Update Posted: June 13, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Colorado, Denver:
areal bone mineral density
dehydroepiandrosterone (DHEA)
postmenopause
exercise
sex hormones
Additional relevant MeSH terms:
Layout table for MeSH terms
Dehydroepiandrosterone
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs