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Recruiting NCT06041789

Effect of Acetylcholinesterase Inhibitors on Bone Metabolism

Phase II Interventional Osteoporosis

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Donepezil, Memantine.
Who it may be relevant to
Registry conditions: Osteoporosis. Basic parameters: from 50 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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

  • Drug Donepezil
    10 mg tablet
  • Drug Memantine
    10 mg tablet

Primary outcome measures

  • Change in bone mineral density, as measured by dual x-ray absorptiometry (DXA) [Time frame: baseline, 12 months]
Secondary outcome measures (3)
  • Change in bone resorption marker C-terminal telopeptide (CTX) [Time frame: baseline, 6 months, 12 months]
  • Change in bone formation marker amino-terminal propeptide of type I procollagen (P1NP) [Time frame: baseline, 6 months, 12 months]
  • Change in Trabecular Bone score [Time frame: baseline, 12 months]

Eligibility criteria

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • 1-year mortality > 25%, measured by ePrognosis calculator
  • Planning to move out of the area in the next 12-months
  • Planning surgery in the next 12-months

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

United States · 1 center
  • Duke Memory Disorders Clinic — Durham

Publications

  • North R, Liu AJ, Pieper C, Danus S, Thacker CR, Ashner M, Colon-Emeric C, Lee RH. Effect of donepezil on bone metabolism among older adults with Alzheimer's disease. Contemp Clin Trials. 2025 Jan;148:107748. doi: 10.1016/j.cct.2024.107748. Epub 2024 Nov 19. PMID 39566720

Identifiers

NCT: NCT06041789 · Pro00111080 · R21AG078982

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗