Osteoporosis, Age-RelatedEarly Phase 1NCT02467400
Dose Response and Receptor Selectivity of Beta-blocker Effects on Bone Metabolism
A Early Phase 1 study testing Atenolol, Nebivolol and Propranolol in people with Osteoporosis, Age-Related, run by Mayo Clinic at 1 site in United States.
Trial summary
This study is designed to answer the question as to whether the sympathetic nervous system is an important determinant of bone metabolism in humans. Read more about this study
- Who is it for?
- Ages 50 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Osteoporosis, Age-Related
- What is being tested?
- Atenolol, Nebivolol and Propranolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 165 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2015to 1 Apr 2018
- Phase
- Early Phase 1
- 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 50 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- at least 5 yrs since their last menses
- Follicle Stimulating Hormone (FSH) > 20 IU/L
Who cannot join
- Abnormality in any of the screening laboratory studies
- Presence of significant liver or renal disease
- Malignancy (including myeloma)
- Malabsorption
- Diabetes
- Hypoparathyroidism
Show all 27Show fewer
- Hyperparathyroidism
- Acromegaly
- Cushing's syndrome
- Hypopituitarism
- Severe chronic obstructive pulmonary disease
- Undergoing treatment with any medications that affect bone turnover, including the following:
- adrenocorticosteroids (> 3 months at any time or > 10 days within the previous yr)
- anticonvulsant therapy (within the previous year)
- pharmacological doses of thyroid hormone (causing decline of thyroid stimulating hormone below normal)
- calcium supplementation of > 1200 mg/d (within the preceding 3 months)
- bisphosphonates (within the past 3 yrs)
- denosumab
- estrogen (E) therapy within the past year
- treatment with a selective E receptor modulator within the past year
- teriparatide within the past yr
- anti-hypertensive therapy
- Clinical history of osteoporotic fracture (vertebral, hip, or distal forearm
- Recent (within the past 6 months) fracture
- Serum 25-hydroxyvitamin D levels of < 20 ng/ml
- Resting blood pressure >140/90 mm Hg or those with hypotension (systolic blood pressure <110 mm Hg), heart rate < 60 bpm
- History of asthma
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
This study is designed to answer the question as to whether the sympathetic nervous system is an important determinant of bone metabolism in humans.
Read the detailed description
In postmenopausal women, who have increased sympathetic outflow, to test the hypothesis that treatment with low doses of a non-selective β-blocker (propranolol) will increase serum markers of bone formation and reduce markers of bone resorption (Aim 1a); and using increasingly β1-AR (adrenergic receptor) selective blockers (atenolol and nebivolol), to better define the β-adrenergic receptor selectivity (β1 versus β2) in the regulation of bone turnover by sympathetic outflow in humans.
- Conditions
- Osteoporosis, Age-Related
- Being tested
- Atenolol, Nebivolol, Propranolol, placebo
- Keywords
- bone formation
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtenololDrug
beta blocker
NebivololDrug
beta blocker
PropranololDrug
beta blocker
placeboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | Sugar pill 2/day for 20 weeks; The once daily groups will receive a placebo as the second dose Receives: Drug: placebo |
| Atenolol | Active comparator | Atenolol 50 mg 1/day for 20 weeks Receives: Drug: Atenolol |
| Nebivolol | Active comparator | Nebivolol 5 mg/day for 20 weeks Receives: Drug: Nebivolol |
| Propranolol 40 mg | Active comparator | Propranolol 20 mg bid for 20 weeks Receives: Drug: Propranolol |
| Propranolol 80 mg | Active comparator | Propranolol 40 mg bid for 20 weeks Receives: Drug: Propranolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of serum bone formation to bone resorption marker
Serum bone formation marker (PINP)/serum bone resorption marker (CTX)
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2015 (estimated)
- Study start1 Jul 2015
- Primary completion26 Oct 2017
- Study completion1 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Osteoporosis, Age-RelatedStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sundeep Khosla, M.D., Mayo Clinic
- Investigators
- Sundeep Khosla, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02467400
- Sponsor's protocol ID
- 14-004305
- Status last verified
- Feb 2019
- First submitted
- 4 Jun 2015
- Last updated
- 6 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Khosla S, Drake MT, Volkman TL, Thicke BS, Achenbach SJ, Atkinson EJ, Joyner MJ, Rosen CJ, Monroe DG, Farr JN. Sympathetic beta1-adrenergic signaling contributes to regulation of human bone metabolism. J Clin Invest. 2018 Nov 1;128(11):4832-4842. doi: 10.1172/JCI122151. Epub 2018 Oct 2.
PubMed 30153111
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Response and Receptor Selectivity of Beta-blocker Effects on Bone Metabolism
- ClinicalTrials.gov ID
- NCT02467400
- Acronym / sponsor ID
- 14-004305
- Conditions
- Osteoporosis, Age-Related
- Keywords
- bone formation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 1 Jul 2015 (actual)
- Primary completion
- 26 Oct 2017 (actual)
- Study completion
- 1 Apr 2018 (actual)
- First posted
- 10 Jun 2015 (estimated)
- 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.
This study is designed to answer the question as to whether the sympathetic nervous system is an important determinant of bone metabolism in humans.
Detailed description
In postmenopausal women, who have increased sympathetic outflow, to test the hypothesis that treatment with low doses of a non-selective β-blocker (propranolol) will increase serum markers of bone formation and reduce markers of bone resorption (Aim 1a); and using increasingly β1-AR (adrenergic receptor) selective blockers (atenolol and nebivolol), to better define the β-adrenergic receptor selectivity (β1 versus β2) in the regulation of bone turnover by sympathetic outflow in humans.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Drug: placeboSugar pill 2/day for 20 weeks; The once daily groups will receive a placebo as the second dose |
| Atenolol | Active comparator | Drug: AtenololAtenolol 50 mg 1/day for 20 weeks |
| Nebivolol | Active comparator | Drug: NebivololNebivolol 5 mg/day for 20 weeks |
| Propranolol 40 mg | Active comparator | Drug: PropranololPropranolol 20 mg bid for 20 weeks |
| Propranolol 80 mg | Active comparator | Drug: PropranololPropranolol 40 mg bid for 20 weeks |
Who may qualify
- Ages
- 50 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
Key exclusion criteria (27 listed)
- adrenocorticosteroids (> 3 months at any time or > 10 days within the previous yr)
- anticonvulsant therapy (within the previous year)
- pharmacological doses of thyroid hormone (causing decline of thyroid stimulating hormone below normal)
- calcium supplementation of > 1200 mg/d (within the preceding 3 months)
- bisphosphonates (within the past 3 yrs)
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 |
|---|---|---|
| Atenololbeta blocker | Drug | Atenolol |
| Nebivololbeta blocker | Drug | Nebivolol |
| Propranololbeta blocker | Drug | Propranolol 40 mg, Propranolol 80 mg |
| placeboplacebo | Drug | placebo |
Primary outcome
Ratio of serum bone formation to bone resorption marker
Time frame: 20 weeks
Serum bone formation marker (PINP)/serum bone resorption marker (CTX)
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 6 Feb 2019.
- Derived from this study: PubMed 30153111Khosla S, Drake MT, Volkman TL, Thicke BS, Achenbach SJ, Atkinson EJ, Joyner MJ, Rosen CJ, Monroe DG, Farr JN. Sympathetic beta1-adrenergic signaling contributes to regulation of human bone metabolism. J Clin Invest. 2018 Nov 1;128(11):4832-4842. doi: 10.1172/JCI122151. Epub 2018 Oct 2.
- 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.
Sundeep Khosla, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Atenolol, Nebivolol and Propranolol in people with Osteoporosis, Age-Related, run by Mayo Clinic 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 2 inclusion and 27 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 6 Feb 2019. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Ratio of serum bone formation to bone resorption marker (time frame: 20 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02467400, which also lists 1 linked publication.
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 6 Feb 2019.