Effect of Acetylcholinesterase Inhibitors on Bone Metabolism

NCT06041789 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: Pro00111080R21AG078982
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (1)

• Change in bone mineral density, as measured by dual x-ray absorptiometry (DXA)

  baseline, 12 months

Secondary Outcomes (3)

• Change in bone resorption marker C-terminal telopeptide (CTX)

  baseline, 6 months, 12 months

• Change in bone formation marker amino-terminal propeptide of type I procollagen (P1NP)

  baseline, 6 months, 12 months

• Change in Trabecular Bone score

  baseline, 12 months

Study Arms (2)

Donepezil

EXPERIMENTAL

Drug: Donepezil

Memantine

ACTIVE COMPARATOR

Drug: Memantine

Interventions

Donepezil DRUG

10 mg tablet

Donepezil

Memantine DRUG

10 mg tablet

Memantine

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of cognitive impairment, including clinical assessment, radiographic or laboratory 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

You may not qualify if:

• Currently on acetylcholinesterase inhibitor or memantine
• 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
• Currently on osteoporosis medication (e.g., bisphosphonate, SERM, denosumab, teriparatide, 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 diseases, malabsorption, inflammatory bowel disease, severe liver disease/cirrhosis, hyperthyroidism (endogenous or exogenous)
• 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
• year mortality \> 25%, measured by ePrognosis calculator

Sponsors & Collaborators

• Duke University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Duke Memory Disorders Clinic

Durham, North Carolina, 27705, United States

RECRUITING

MeSH Terms

Conditions

Osteoporosis

Interventions

Donepezil; Memantine

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Amantadine; Adamantane; Bridged-Ring Compounds

Study Officials

• Richard H Lee, MD, MPH

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Susanne Danus

CONTACT

(919) 681-9807; susanne.danus@duke.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2023
• First Posted: September 18, 2023
• Study Start: February 3, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)