DHEA Augmentation of Musculoskeletal Adaptations to Exercise in Older Women

NCT03227458 | Completed DMC

• 2 other identifiers: 16-24275R01AG053489-05
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

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.

Conditions

Low Bone Mass; Osteoporosis, Postmenopausal

Keywords

areal bone mineral density; dehydroepiandrosterone (DHEA); postmenopause; exercise; sex hormones

Outcome Measures

Primary Outcomes (1)

• Change in lumbar spine aBMD

  mean change from baseline in lumbar spine aBMD

  Baseline and 36 Weeks

Secondary Outcomes (13)

• Change in total hip aBMD

  36 Weeks

• Change in regional hip aBMD

  Baseline and 36 Weeks

• Change in Vertebral (L1-2) total volumetric bone mineral density (vBMD)

  Baseline and 36 Weeks

• Change in Vertebral (L1-2) cortical vBMD

  Baseline and 36 Weeks

• Change in Vertebral (L1-2) trabecular vBMD

  Baseline and 36 Weeks

Study Arms (3)

Exercise and DHEA

ACTIVE COMPARATOR

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; Behavioral: Exercise

Exercise and Placebo

ACTIVE COMPARATOR

1 study pill containing placebo daily for 36 weeks and supervised bone-loading exercise on 3 days per week for 36 weeks.

Other: Placebo; Behavioral: Exercise

DHEA only

ACTIVE COMPARATOR

1 study pill containing 50 mg of DHEA daily for 36 weeks

Other: DHEA

Interventions

DHEA OTHER

Participants will take 1 study pill (50 mg DHEA) daily for 36 weeks.

Also known as: DHEA therapy

DHEA only; Exercise and DHEA

Placebo OTHER

Participants will take placebo daily for 36 weeks.

Exercise and Placebo

Exercise BEHAVIORAL

bone-loading exercise on 3 days per week for 38 weeks

Also known as: bone-loading exercise

Exercise and DHEA; Exercise and Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• non-frail, as determined by short physical performance battery (SPPB) score \> 9 (0-12 scale);
• 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

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Osteoporosis, Postmenopausal; Motor Activity

Interventions

Dehydroepiandrosterone; Exercise

Condition Hierarchy (Ancestors)

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavior

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 17-Ketosteroids; Ketosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Catherine Jankowski, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Study drug will be masked. 50 mg DHEA or placebo: double-blinded. Exercise will not be masked.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 20, 2017
• First Posted: July 24, 2017
• Study Start: February 12, 2018
• Primary Completion: June 19, 2024
• Study Completion: June 19, 2024
• Last Updated: December 5, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)