Effect of Acetylcholinesterase Inhibitors on Bone Metabolism

Osteoporosis Clinical Trial

Official title:

Effect of Acetylcholinesterase Inhibitors on Bone Metabolism and Fracture Risk Factors Among Older Adults With Mild to Moderate Alzheimer's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06041789
• Other study ID #: Pro00111080
• Secondary ID: R21AG078982
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2024
• Est. completion date: June 2025

Study information

• Verified date: May 2024
• Source: Duke University
• Contact: Connie Thacker
• Phone: (919) 681-9807
• Email: connie.thacker[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 45
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• Donepezil
10 mg tablet
• Placebo
Donepezil placebo tablet

Locations

Country	Name	City	State
United States	Duke Memory Disorders Clinic	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in bone mineral density, as measured by dual x-ray absorptiometry (DXA)		baseline, 12 months
Secondary	Change in bone resorption marker C-terminal telopeptide (CTX)	measured using commercially available ELISA test on serum	baseline, 6 months, 12 months
Secondary	Change in bone formation marker amino-terminal propeptide of type I procollagen (P1NP)	measured using commercially available ELISA test on serum	baseline, 6 months, 12 months
Secondary	Change in Trabecular Bone score	measure of bone quality, using DXA spine images	baseline, 12 months