DHEA Augmentation of Musculoskeletal Adaptations to Exercise in Older Women

• ClinicalTrials.gov Identifier: NCT03227458
• Recruitment Status: Recruiting
• First Posted: July 24, 2017
• Last Update Posted: March 14, 2023
• Sponsor: University of Colorado, Denver
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

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) or moderate osteoporosis (T-scores < -2.5 and >= -3.0) and by restoring serum DHEAS to young adult levels by oral DHEA replacement.

Condition or disease	Intervention/treatment	Phase
Low Bone Mass; Osteoporosis, Postmenopausal	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.

Study Design

• 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: February 12, 2018
• Estimated Primary Completion Date: April 2024
• Estimated Study Completion Date: April 2024

Arms and Interventions

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

Outcome Measures

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 volumetric bone mineral density (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

Eligibility Criteria

• Ages Eligible for Study: 55 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 or moderate osteoporosis defined as lumbar spine or proximal hip aBMD t-scores < -1.0 and > = -3.0;
• refusal of standard osteoporosis treatment in women with moderate osteoporosis (BMD t-scores >=-3.0 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
• normal cognitive function, as determined by a Mini-Cog score > = 4

Exclusion Criteria:

• history of hospitalization for Corona Virus Disease-19 (COVID-19)
• does not meet Centers for Disease Control and Prevention (CDC) recommendations for home isolation because has had a positive severe acute respiratory syndrome corona virus-2 (SARS-COV-2) test less than 10 days before study entry; or has had fever within the past 3 days and respiratory symptoms have not improved; or symptoms first appeared less than 10 days before study entry
• uncontrolled hypertension defined as resting systolic blood pressure (sBP) >150 mmHg or diastolic blood pressure (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 ≥ 4 liters 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;
• hematocrit (HCT) > 54%;
• thyroid dysfunction, defined as an ultrasensitive thyroid stimulating hormone (TSH) < 0.4 or > 10.0 microunits/mL;, without signs or symptoms of clinical hypo- or hyperthyroidism. 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) ≥ 1.5 times the upper limits of normal;
• estimated glomerular filtration rate (eGFR) < 45, using the Modification of Diet in Renal Disease (MDRD) equation (Levey et al, Annals Inter Med, 1999; Munter et al, Clin J Am Soc Nephrology, 2009);
• poorly controlled diabetes mellitus based on HbA1c > 8.5%, or use of insulin;
• fasted serum triglycerides > 400 mg/dL;
• serum 25-hydroxy 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 per the study's vitamin D repletion protocol.
• use of DHEA supplementation or sex hormones in the past 6 months. Use of prescription low dose vaginal estrogen creams (Premarin or Estrace) 3 days per week will not be exclusionary.
• 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)
• use of insulin;
• lumbar spine, total hip, or femoral neck aBMD t-scores < -3.0;
• secondary osteoporosis

Contacts and Locations

Contacts

Contact: Catherine Jankowski, PhD; 303-724-7383; catherine.jankowski@cuanschutz.edu

Locations

United States, Colorado

University of Colorado Anschutz Medical Campus; Recruiting

Aurora, Colorado, United States, 80045

Contact: Catherine Jankowski, PhD 303-724-7383 catherine.jankowski@cuanschutz.edu

Principal Investigator: Catherine Jankowski, PhD

Sponsors and Collaborators

University of Colorado, Denver

National Institute on Aging (NIA)

Investigators

• Principal Investigator: Catherine Jankowski, PhD; University of Colorado, Denver

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03227458
• Other Study ID Numbers: 16-2427; R01AG053489 ( U.S. NIH Grant/Contract )
• First Posted: July 24, 2017
• Last Update Posted: March 14, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Osteoporosis; Osteoporosis, Postmenopausal; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Dehydroepiandrosterone; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs