Osteoporosis
Conditions
Brief 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. 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 randomly assigned to donepezil or matching memantine 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.
Interventions
DRUGDonepezil
10 mg tablet
DRUGMemantine
10 mg tablet
Sponsors
National Institute on Aging (NIA)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of cognitive impairment, including clinical assessment, radiographic or laboratory biomarker assessment 2. Willing to initiate treatment for cognitive impairment 3. 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 4. Geriatric Depression Scale score \< 6 5. English-speaking
Exclusion criteria
1. Currently on acetylcholinesterase inhibitor or memantine 2. History of bradycardia, heart block, long QT, unexplained syncope, or other contraindication 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 3. Currently on osteoporosis medication (e.g., bisphosphonate, SERM, denosumab, teriparatide, abaloparatide, romozosumab, calcitonin) 4. Use of bisphosphonate within last 5 years 5. Use within last 6 months of estrogens or testosterone, androgen deprivation therapy or aromatase inhibitors, antiepileptic, heparin therapy, thiazolidinediones 6. History of disorders associated with secondary osteoporosis: collagen vascular diseases, malabsorption, inflammatory bowel disease, severe liver disease/cirrhosis, hyperthyroidism (endogenous or exogenous) 7. History of fracture of the humerus, wrist, or vertebra due to fall from standing height or less 8. History of hip fracture, hip replacement, or non-ambulatory 9. Long-term use (\>6 months) of corticosteroids 10. History of Parkinson's, HIV, Huntington's disease 11. History of solid organ transplantation 12. 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 13. Severe kidney impairment (eGFR \< 30 ml/min), 14. Active malignancy currently undergoing chemotherapeutic, surgical, or radiation therapy, except non-melanomatous skin cancer 15. 1-year mortality \> 25%, measured by ePrognosis calculator 16. Planning to move out of the area in the next 12-months 17. Planning surgery in the next 12-months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in bone mineral density, as measured by dual x-ray absorptiometry (DXA) | baseline, 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in bone resorption marker C-terminal telopeptide (CTX) | baseline, 6 months, 12 months | measured using commercially available ELISA test on serum |
| Change in bone formation marker amino-terminal propeptide of type I procollagen (P1NP) | baseline, 6 months, 12 months | measured using commercially available ELISA test on serum |
| Change in Trabecular Bone score | baseline, 12 months | measure of bone quality, using DXA spine images |
Countries
United States
Contacts
Primary ContactSusanne Danus
Outcome results
None listed