Low Bone DensityNCT05316272
Effects of DHEA and Exercise on Bone Marrow Fat in Postmenopausal Women
A study testing Exercise and DHEA in people with Low Bone Density and Osteoporosis, run by University of Colorado, Denver at 1 site in United States.
Trial summary
Bone strength -the main determinant of bone fracture- is a function not only of bone mineral density (BMD) and microstructure, but also of its microenvironment, including bone marrow fat (BMF). Read more about this study
- Who is it for?
- Ages 55 to 85 years, women only
- Conditions the study is for
- Low Bone Density, Osteoporosis
- What is being tested?
- Exercise and DHEA
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Mar 2022to 30 Jun 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- women aged 55 to 85 years
- non-frail, as determined by Short Physical Performance Battery 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 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
Show all 28Show fewer
- ambulatory without assistive devices
- serum DHEAS < 140 μg/dL (3.8 μmol/L)
- low bone mass or moderate osteoporosis indicated by lumbar spine, total hip, or femoral neck aBMD t-scores < -1.0 and ≥ -3.0
- refusal of standard osteoporosis treatment in women with moderate osteoporosis (BMD ≥-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
- willing to provide evidence of completed COVID-19 vaccination
- no implanted metal or electronic devices
- no metallic foreign body in the eye
- no "triggerfish" contact lenses
- no gastric reflux device
- no insulin pumps
- no temporary transvenous pacing leads
- no aneurysm clips
- no cardiac pacemakers
- no implanted cardioverter defibrillator
- no magnetically-activated implant or device
- no neurostimulation system
- no spinal cord stimulator
- no cochlear implant
- no bone growth/bone fusion stimulator
- no known claustrophobia
Who cannot join
- history of hospitalization for Corona Virus Disease 2019 (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 coronavirus 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.
- not willing to provide evidence of completed COVID-19 vaccination.
- uncontrolled hypertension defined as resting systolic BP >150 mmHg or diastolic BP >90 mmHg; participants who do not meet these criteria at first screening will be re-evaluated, including follow-up evaluation by their primary care provider (PCP) with initiation or adjustment of anti-hypertensive medications.
- diagnosed ischemic heart disease or indicators of unstable ischemic heart disease (e.g., angina) or arrhythmias at rest or during the graded 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.
Show all 30Show fewer
- 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 > 54%
- thyroid dysfunction, defined as an ultrasensitive thyroid stimulating hormone (TSH) < 0.4 or > 10 micro units/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 (ALT, aspartate aminotransferase, alkaline phosphatase) ≥ 1.5 times the upper limits of normal
- estimated glomerular filtration rate (eGFR) < 45, using Modification of Diet in Renal Disease Study (MDRD) equation
- 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 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 or less 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)
- lumbar spine, total hip, or femoral neck aBMD t-scores < -3.0.
- confirmed history of osteoporotic fracture
- secondary osteoporosis
- 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
- undiagnosed vaginal bleeding
- women who, in the judgment of the study physician, appear incapable of safely participating in the exercise (e.g., neuromuscular/musculoskeletal impairment).
- Known claustrophobia if participating in the optional MRI study
- No metal implants (detailed above) if participating in the optional MRI study
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
Bone strength -the main determinant of bone fracture- is a function not only of bone mineral density (BMD) and microstructure, but also of its microenvironment, including bone marrow fat (BMF). The adrenal steroid dehydroepiandrosterone (DHEA) -the main precursor for estrogens and androgens in postmenopausal women- as well as bone-loading exercise, increase BMD in older women, however, their effects on BMF are largely unknown. This study has high potential to unveil the hormonal and mechanical effects of DHEA and exercise on BMF, respectively, and to elucidate longitudinal associations of BMF with bone strength in older women with bone loss.
Read the detailed description
The proportion of the U.S. population older than 65 years will increase from 12.7% in 2000 to 20.3% in 2050, and the number of fractures is expected to exceed 3 million by 2025 with associated costs in the order of $25.3 billion per year. DAMES is an ongoing clinical trial (NCT03227458) that aims to assess -for the first time- changes in areal bone mineral density (aBMD) and fat-free mass (FFM) in response to therapy with the adrenal steroid dehydroepiandrosterone (DHEA) alone and combined with bone-loading exercise (EX) in older women with bone loss. The hormonal and mechanical strategies proposed in DAMES represent a low-cost alternative treatment to improve bone quantity with a number of other health benefits not afforded by typical pharmacological approaches. However, bone strength -the main determinant of bone fracture- is a function of not only BMD and microstructure, but also of its microenvironment, including bone marrow fat (BMF). This in an ancillary study to the DAMES clinical trial. Here, the investigators propose to leverage the well-characterized cohort of subjects, exercise training, clinical, laboratory and imaging data from DAMES, and add a small group of controls to its three existing arms (DHEA only, EX+Placebo, and EX+DHEA) to investigate the effects of DHEA therapy and EX on BMF in older women using advanced imaging, numerical engineering, and image analysis techniques. In particular, the investigators aim to determine in the lumbar spine and hip of older women with low bone mass or moderate osteoporosis: 1) whether DHEA or EX leads to changes in BMF content; 2) whether BMF content is associated with bone strength at baseline, and whether changes in BMF content are associated with changes in bone strength, evaluating the impact of DHEA or EX on these associations; and 3) the spatial distribution of changes in BMF content in response to DHEA or EX. BMF will be measured with chemical shift-based water-fat separation magnetic resonance imaging, bone strength will be estimated with finite element modeling from quantitative computed tomography scans, and differences in the spatial distribution of BMF changes between groups will be assessed using voxel-based morphometry. Ultimately, the investigators will leverage the DAMES clinical trial to unveil new information to improve our understanding of DHEA and EX on bone quantity and quality. The longitudinal assessments of bone quality in this ancillary proposal, with those of bone quantity in the parent study, in women who have already lost bone mass is unprecedented. Understanding how osteoporosis treatments -including exercise- act on BMF could lead to the generation of novel approaches for fracture risk assessment, procedures for therapy monitoring, and treatments for bone loss.
- Conditions
- Low Bone Density, Osteoporosis
- Being tested
- Exercise, DHEA
- Medical subject headings
- Bone Diseases, Metabolic, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExerciseBehavioural
Supervised bone-loading exercise on 3 days per week for 36 weeks
DHEADietary supplement
DHEA in pill form 50 milligrams taken daily for 36 weeks
| Study group | Role | What they receive |
|---|---|---|
| Exercise and placebo | Experimental | supervised bone-loading exercise 3 days per week and one placebo pill per day for 36 weeks Receives: Behavioral: Exercise; Dietary Supplement: DHEA |
| Exercise and DHEA | Experimental | supervised bone-loading exercise 3 days per week and one dose of DHEA (50 milligrams) per day for 36 weeks Receives: Behavioral: Exercise; Dietary Supplement: DHEA |
| no exercise and DHEA | Experimental | no supervised bone exercise and one dose of DHEA (50 milligrams) per day for 36 weeks Receives: Behavioral: Exercise; Dietary Supplement: DHEA |
| no exercise and placebo | Experimental | no supervised bone-loading exercise and one placebo pill per day for 36 weeks Receives: Behavioral: Exercise; Dietary Supplement: DHEA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in spine bone marrow fat content
changes in bone marrow fat content of the lumbar spine
Measured: 36 weeks
Changes in hip bone marrow fat content
changes in bone marrow fat content of the proximal femur
Measured: 36 weeks
Correlation of lumbar spine bone marrow fat content with bone strength at baseline
Correlation of lumbar bone marrow fat content (%) with strength (N) of the lumbar spine at baseline
Measured: baseline - 0 weeks of intervention
Correlation of hip bone marrow fat content with hip strength at baseline
Correlation of proximal femur spine bone marrow fat content (%) with strength (N) of the proximal femur at baseline
Measured: baseline - 0 weeks of intervention
Correlation of the changes in spine bone marrow fat content with changes in spine bone strength
Correlation of the changes in lumbar spine bone marrow fat content (%) with changes in lumbar spine strength (N)
Measured: 36 weeks
Correlation of the changes in hip bone marrow fat content (%) with changes in hip bone strength (N)
Correlation of the changes in proximal femur bone marrow fat content (%) with changes in proximal femur bone strength (N)
Measured: 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2022
- Study start11 Mar 2022
- Primary completion30 Jun 2024
- Study completion30 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Low Bone DensityStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- Two-by-two crossed design of DHEA versus control and exercise versus no exercise control.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor
- Investigators
- Catherine Jankowski, PhD, Principal investigator, University of Colorado, DenverJulio Carballido-Gamio, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05316272
- Sponsor's protocol ID
- 162427a
- Other IDs
- 5R01AR077924-03
- Status last verified
- Dec 2024
- First submitted
- 17 Mar 2022
- Last updated
- 10 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of DHEA and Exercise on Bone Marrow Fat in Postmenopausal Women
- ClinicalTrials.gov ID
- NCT05316272
- Acronym / sponsor ID
- 162427a
- Conditions
- Low Bone Density, Osteoporosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- 11 Mar 2022 (actual)
- Primary completion
- 30 Jun 2024 (actual)
- Study completion
- 30 Jun 2024 (actual)
- First posted
- 7 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Bone strength -the main determinant of bone fracture- is a function not only of bone mineral density (BMD) and microstructure, but also of its microenvironment, including bone marrow fat (BMF). The adrenal steroid dehydroepiandrosterone (DHEA) -the main precursor for estrogens and androgens in postmenopausal women- as well as bone-loading exercise, increase BMD in older women, however, their effects on BMF are largely unknown. This study has high potential to unveil the hormonal and mechanical effects of DHEA and exercise on BMF, respectively, and to elucidate longitudinal associations of BMF with bone strength in older women with bone loss.
Detailed description
The proportion of the U.S. population older than 65 years will increase from 12.7% in 2000 to 20.3% in 2050, and the number of fractures is expected to exceed 3 million by 2025 with associated costs in the order of $25.3 billion per year. DAMES is an ongoing clinical trial (NCT03227458) that aims to assess -for the first time- changes in areal bone mineral density (aBMD) and fat-free mass (FFM) in response to therapy with the adrenal steroid dehydroepiandrosterone (DHEA) alone and combined with bone-loading exercise (EX) in older women with bone loss. The hormonal and mechanical strategies proposed in DAMES represent a low-cost alternative treatment to improve bone quantity with a number of other health benefits not afforded by typical pharmacological approaches. However, bone strength -the main determinant of bone fracture- is a function of not only BMD and microstructure, but also of its microenvironment, including bone marrow fat (BMF). This in an ancillary study to the DAMES clinical trial. Here, the investigators propose to leverage the well-characterized cohort of subjects, exercise training, clinical, laboratory and imaging data from DAMES, and add a small group of controls to its three existing arms (DHEA only, EX+Placebo, and EX+DHEA) to investigate the effects of DHEA therapy and EX on BMF in older women using advanced imaging, numerical engineering, and image analysis techniques. In particular, the investigators aim to determine in the lumbar spine and hip of older women with low bone mass or moderate osteoporosis: 1) whether DHEA or EX leads to changes in BMF content; 2) whether BMF content is associated with bone strength at baseline, and whether changes in BMF content are associated with changes in bone strength, evaluating the impact of DHEA or EX on these associations; and 3) the spatial distribution of changes in BMF content in response to DHEA or EX. BMF will be measured with chemical shift-based water-fat separation magnetic resonance imaging, bone strength will be estimated with finite element modeling from quantitative computed tomography scans, and differences in the spatial distribution of BMF changes between groups will be assessed using voxel-based morphometry. Ultimately, the investigators will leverage the DAMES clinical trial to unveil new information to improve our understanding of DHEA and EX on bone quantity and quality. The longitudinal assessments of bone quality in this ancillary proposal, with those of bone quantity in the parent study, in women who have already lost bone mass is unprecedented. Understanding how osteoporosis treatments -including exercise- act on BMF could lead to the generation of novel approaches for fracture risk assessment, procedures for therapy monitoring, and treatments for bone loss.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Two-by-two crossed design of DHEA versus control and exercise versus no exercise control.
| Arm | Type | Receives |
|---|---|---|
| Exercise and placebo | Experimental | Behavioral: Exercise, Dietary Supplement: DHEAsupervised bone-loading exercise 3 days per week and one placebo pill per day for 36 weeks |
| Exercise and DHEA | Experimental | Behavioral: Exercise, Dietary Supplement: DHEAsupervised bone-loading exercise 3 days per week and one dose of DHEA (50 milligrams) per day for 36 weeks |
| no exercise and DHEA | Experimental | Behavioral: Exercise, Dietary Supplement: DHEAno supervised bone exercise and one dose of DHEA (50 milligrams) per day for 36 weeks |
| no exercise and placebo | Experimental | Behavioral: Exercise, Dietary Supplement: DHEAno supervised bone-loading exercise and one placebo pill per day for 36 weeks |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- women aged 55 to 85 years
- non-frail, as determined by Short Physical Performance Battery 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 take DHEA (50mg/d) or a placebo pill daily and remain blinded for up to 36 weeks
Key exclusion criteria (30 listed)
- history of hospitalization for Corona Virus Disease 2019 (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 coronavirus 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.
- not willing to provide evidence of completed COVID-19 vaccination.
- uncontrolled hypertension defined as resting systolic BP >150 mmHg or diastolic BP >90 mmHg; participants who do not meet these criteria at first screening will be re-evaluated, including follow-up evaluation by their primary care provider (PCP) with initiation or adjustment of anti-hypertensive medications.
- diagnosed ischemic heart disease or indicators of unstable ischemic heart disease (e.g., angina) or arrhythmias at rest or during the graded 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ExerciseSupervised bone-loading exercise on 3 days per week for 36 weeks | Behavioural | Exercise and DHEA, Exercise and placebo, no exercise and DHEA, no exercise and placebo |
| DHEADHEA in pill form 50 milligrams taken daily for 36 weeks | Dietary supplement | Exercise and DHEA, Exercise and placebo, no exercise and DHEA, no exercise and placebo |
Primary outcome
Changes in spine bone marrow fat content
Time frame: 36 weeks
changes in bone marrow fat content of the lumbar spine
Changes in hip bone marrow fat content
Time frame: 36 weeks
changes in bone marrow fat content of the proximal femur
Correlation of lumbar spine bone marrow fat content with bone strength at baseline
Time frame: baseline - 0 weeks of intervention
Correlation of lumbar bone marrow fat content (%) with strength (N) of the lumbar spine at baseline
Correlation of hip bone marrow fat content with hip strength at baseline
Time frame: baseline - 0 weeks of intervention
Correlation of proximal femur spine bone marrow fat content (%) with strength (N) of the proximal femur at baseline
Correlation of the changes in spine bone marrow fat content with changes in spine bone strength
Time frame: 36 weeks
Correlation of the changes in lumbar spine bone marrow fat content (%) with changes in lumbar spine strength (N)
Correlation of the changes in hip bone marrow fat content (%) with changes in hip bone strength (N)
Time frame: 36 weeks
Correlation of the changes in proximal femur bone marrow fat content (%) with changes in proximal femur bone strength (N)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catherine Jankowski, PhD principal investigator
University of Colorado, Denver
Julio Carballido-Gamio, PhD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise and DHEA in people with Low Bone Density and Osteoporosis, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in spine bone marrow fat content (time frame: 36 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2024.