Clinical trial NCT06041789: Effect of Acetylcholinesterase Inhibitors on Bone Metabolism
Official title: Effect of Acetylcholinesterase Inhibitors on Bone Metabolism and Fracture Risk Factors Among Older Adults With Mild to Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Osteoporosis
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2023-09-18
Enrollment: 45
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 placebo 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.


Eligibility criteria: Inclusion Criteria:

1. Diagnosis of ADRD, including clinical assessment and either radiographic or laboratory biomarker assessment
2. Meets NIA-AA clinical dementia criteria
3. Willing to initiate treatment with AchEI for ADRD
4. MoCA score \< 24
5. For females, either age \> 55 years, or Age \< 55 years and at least 12 months since last menstrual period
6. For males, age \> 50 years
7. Geriatric Depression Scale score \< 6

Exclusion Criteria:

1. Currently on acetylcholinesterase inhibitor
2. Currently on osteoporosis medication (e.g., bisphosphonate, SERM, denosumab, teripar-atide, abaloparatide, romozosumab)
3. Use of bisphosphonate within last 2 years
4. Use within last 6 months of estrogens or testosterone, androgen deprivation therapy or aromatase inhibitors, antiepileptic, heparin therapy, thiazolidinediones
5. History of disorders associated with osteoporosis: collagen vascular diseases, malab-sorption, inflammatory bowel disease, severe liver disease/cirrhosis, hyperthyroidism (endogenous or exogenous)
6. History of hip fracture, hip replacement, or non-ambulatory
7. Long-term use (\>6 months) of corticosteroids
8. History of Parkinson's, HIV, Huntington's disease
9. History of solid organ transplantation
10. Severe kidney impairment (eGFR \< 30 ml/sec),
11. Active malignancy, except non-melanomatous skin cancer
12. 1-year mortality \> 25%, measured by ePrognosis calculator
13. Initiation of investigational or FDA-approved anti-amyloid drug

Primary outcomes:
measure: Change in bone mineral density, as measured by dual x-ray absorptiometry (DXA)
timeFrame: baseline, 12 months
Secondary outcomes:
measure: Change in bone resorption marker C-terminal telopeptide (CTX)
timeFrame: baseline, 6 months, 12 months
measure: Change in bone formation marker amino-terminal propeptide of type I procollagen (P1NP)
timeFrame: baseline, 6 months, 12 months
measure: Change in Trabecular Bone score
timeFrame: baseline, 12 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Memory Disorders Clinic
state: North Carolina
Study officials:
affiliation: Duke University
name: Richard H Lee, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: