Effect of Acetylcholinesterase Inhibitors on Bone Metabolism

Phase 2

Recruiting

• Conditions: Osteoporosis
• Interventions: Drug: Placebo; Drug: Donepezil

• Registration Number: NCT06041789
• Lead Sponsor: Duke University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-11
• Study First Submitted QC: 2023-09-11
• Study First Posted: 2023-09-18
• Status Verified: 2024-10
• Study Start: 2025-02-03
• Last Update Submitted: 2025-02-04
• Last Update Posted: 2025-02-05
• Primary Completion: 2025-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Donepezil	Donepezil	-

Primary Outcome Measures

Name	Time	Method
Change in bone mineral density, as measured by dual x-ray absorptiometry (DXA)	baseline, 12 months

Secondary Outcome Measures

Name	Time	Method
Change in Trabecular Bone score	baseline, 12 months	measure of bone quality, using DXA spine images
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

Trial Locations

Locations (1)

Duke Memory Disorders Clinic; 🇺🇸 Durham, North Carolina, United States