OsteoporosisPhase 2NCT06041789
Effect of Acetylcholinesterase Inhibitors on Bone Metabolism
A Phase 2 study testing Donepezil and Memantine in people with Osteoporosis, run by Duke University at 1 site in United States.
Trial summary
People with Alzheimer's disease are at an increased risk of bone fracture. Some studies have shown that those taking donepezil have a lower rate of bone fractures, but the reasons for this are unknown. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Osteoporosis
- What is being tested?
- Donepezil and Memantine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Feb 2025to Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of cognitive impairment, including clinical assessment, radiographic or labora-tory biomarker assessment
- Willing to initiate treatment for cognitive impairment
- A) For females: either age > 55 years, or Age < 55 years and at least 12 months since last menstrual period B) For males, age > 50 years
- Geriatric Depression Scale score < 6
- English-speaking
Who cannot join
- Currently on acetylcholinesterase inhibitor >3 months
- History of bradycardia, heart block, long QT, unexplained syncope, or other contraindica-tion for donepezil; subject with ECG showing HR < 50, PR interval > 200 ms, QTc > 440 ms in men or > 460 ms in women, or evidence of atrioventricular block
- Currently on osteoporosis medication (e.g., bisphosphonate, SERM, denosumab, teripar-atide, abaloparatide, romozosumab, calcitonin)
- Use of bisphosphonate within last 5 years
- Use within last 6 months of estrogens or testosterone, androgen deprivation therapy or aromatase inhibitors, antiepileptic, heparin therapy, thiazolidinediones
- History of disorders associated with secondary osteoporosis: collagen vascular diseas-es, malabsorption, inflammatory bowel disease, severe liver disease/cirrhosis, hyperthy-roidism (endogenous or exogenous)
Show all 17Show fewer
- History of fracture of the humerus, wrist, or vertebra due to fall from standing height or less
- History of hip fracture, hip replacement, or non-ambulatory
- Long-term use (>6 months) of corticosteroids
- History of Parkinson's, HIV, Huntington's disease
- History of solid organ transplantation
- History of bariatric surgery or intending to lose weight by bariatric surgery or weight loss medication (e.g. GLP-1 agonist) in the next 12-months
- Severe kidney impairment (eGFR < 30 ml/min),
- Active malignancy currently undergoing chemotherapeutic, surgical, or radiation therapy, except non-melanomatous skin cancer
- 1-year mortality > 25%, measured by ePrognosis calculator
- Planning to move out of the area in the next 12-months
- Planning surgery in the next 12-months
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Duke Memory Disorders Clinic
Durham, North Carolina, 27705
Connie Thacker
About this study
Official title: Effect of Acetylcholinesterase Inhibitors on Bone Metabolism and Fracture Risk Factors Among Older Adults With Mild to Moderate Alzheimer's Disease
People with Alzheimer's disease are at an increased risk of bone fracture. Some studies have shown that those taking donepezil have a lower rate of bone fractures, but the reasons for this are unknown. The purpose of this study is to measure the effect of donepezil treatment on bone metabolism factors including bone mineral density, bone turnover markers, and bone quality.
Participants in this study will have a bone density test and have blood samples collected at the baseline study visit. Participants will then be assigned to donepezil to be taken daily by mouth for 12 months. Blood samples will be collected at 6 and 12 months. A repeat bone density test will be performed at 12 months. Participants will also complete questionnaires at each study visit.
- Conditions
- Osteoporosis
- Being tested
- Donepezil, Memantine
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonepezilDrug
10 mg tablet
MemantineDrug
10 mg tablet
| Study group | Role | What they receive |
|---|---|---|
| Donepezil | Experimental | Not described Receives: Drug: Donepezil |
| Memantine | Active comparator | Not described Receives: Drug: Memantine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in bone mineral density, as measured by dual x-ray absorptiometry (DXA)
Measured: baseline, 12 months
Secondary outcomes (3)
Change in bone resorption marker C-terminal telopeptide (CTX)
measured using commercially available ELISA test on serum
Measured: baseline, 6 months, 12 months
Change in bone formation marker amino-terminal propeptide of type I procollagen (P1NP)
measured using commercially available ELISA test on serum
Measured: baseline, 6 months, 12 months
Change in Trabecular Bone score
measure of bone quality, using DXA spine images
Measured: baseline, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2023
- Study start3 Feb 2025
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
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 OsteoporosisStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Richard H Lee, MD, MPH, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06041789
- Sponsor's protocol ID
- Pro00111080
- Other IDs
- R21AG078982
- Status last verified
- Aug 2026
- First submitted
- 11 Sep 2023
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
North R, Liu AJ, Pieper C, Danus S, Thacker CR, Ashner M, Colon-Emeric C, Lee RH. Effect of donepezil on bone metabolism among older adults with Alzheimer's disease. Contemp Clin Trials. 2025 Jan;148:107748. doi: 10.1016/j.cct.2024.107748. Epub 2024 Nov 19.
PubMed 39566720
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Acetylcholinesterase Inhibitors on Bone Metabolism and Fracture Risk Factors Among Older Adults With Mild to Moderate Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT06041789
- Acronym / sponsor ID
- Pro00111080
- Conditions
- Osteoporosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 3 Feb 2025 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 18 Sep 2023 (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.
People with Alzheimer's disease are at an increased risk of bone fracture. Some studies have shown that those taking donepezil have a lower rate of bone fractures, but the reasons for this are unknown. The purpose of this study is to measure the effect of donepezil treatment on bone metabolism factors including bone mineral density, bone turnover markers, and bone quality.
Participants in this study will have a bone density test and have blood samples collected at the baseline study visit. Participants will then be assigned to donepezil to be taken daily by mouth for 12 months. Blood samples will be collected at 6 and 12 months. A repeat bone density test will be performed at 12 months. Participants will also complete questionnaires at each study visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donepezil | Experimental | Drug: Donepezil |
| Memantine | Active comparator | Drug: Memantine |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of cognitive impairment, including clinical assessment, radiographic or labora-tory biomarker assessment
- Willing to initiate treatment for cognitive impairment
- A) For females: either age > 55 years, or Age < 55 years and at least 12 months since last menstrual period B) For males, age > 50 years
- Geriatric Depression Scale score < 6
- English-speaking
Key exclusion criteria (17 listed)
- Currently on acetylcholinesterase inhibitor >3 months
- History of bradycardia, heart block, long QT, unexplained syncope, or other contraindica-tion for donepezil; subject with ECG showing HR < 50, PR interval > 200 ms, QTc > 440 ms in men or > 460 ms in women, or evidence of atrioventricular block
- Currently on osteoporosis medication (e.g., bisphosphonate, SERM, denosumab, teripar-atide, abaloparatide, romozosumab, calcitonin)
- Use of bisphosphonate within last 5 years
- Use within last 6 months of estrogens or testosterone, androgen deprivation therapy or aromatase inhibitors, antiepileptic, heparin therapy, thiazolidinediones
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 |
|---|---|---|
| Donepezil10 mg tablet | Drug | Donepezil |
| Memantine10 mg tablet | Drug | Memantine |
Primary outcome
Change in bone mineral density, as measured by dual x-ray absorptiometry (DXA)
Time frame: baseline, 12 months
3 secondary outcomes
Change in bone resorption marker C-terminal telopeptide (CTX)
Time frame: baseline, 6 months, 12 months
Change in bone formation marker amino-terminal propeptide of type I procollagen (P1NP)
Time frame: baseline, 6 months, 12 months
Change in Trabecular Bone score
Time frame: baseline, 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Derived from this study: PubMed 39566720North R, Liu AJ, Pieper C, Danus S, Thacker CR, Ashner M, Colon-Emeric C, Lee RH. Effect of donepezil on bone metabolism among older adults with Alzheimer's disease. Contemp Clin Trials. 2025 Jan;148:107748. doi: 10.1016/j.cct.2024.107748. Epub 2024 Nov 19.
- 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.
Richard H Lee, MD, MPH principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Donepezil and Memantine in people with Osteoporosis, run by Duke University 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 5 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 21 Sep 2026. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Susanne Danus ((919) 681-9807, susanne.danus@duke.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in bone mineral density, as measured by dual x-ray absorptiometry (DXA) (time frame: baseline, 12 months). 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 NCT06041789, 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 21 Sep 2026.