MedPath

Effect of Acetylcholinesterase Inhibitors on Bone Metabolism

Phase 2
Recruiting
Conditions
Osteoporosis
Interventions
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 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
45
Inclusion Criteria
  1. Diagnosis of cognitive impairment, including clinical assessment, radiographic or laboratory biomarker assessment
  2. Willing to initiate treatment for cognitive impairment
  3. 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
  4. Geriatric Depression Scale score < 6
  5. English-speaking
Exclusion Criteria
  1. Currently on acetylcholinesterase inhibitor or memantine
  2. 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
  3. Currently on osteoporosis medication (e.g., bisphosphonate, SERM, denosumab, teriparatide, abaloparatide, romozosumab, calcitonin)
  4. Use of bisphosphonate within last 5 years
  5. Use within last 6 months of estrogens or testosterone, androgen deprivation therapy or aromatase inhibitors, antiepileptic, heparin therapy, thiazolidinediones
  6. History of disorders associated with secondary osteoporosis: collagen vascular diseases, malabsorption, inflammatory bowel disease, severe liver disease/cirrhosis, hyperthyroidism (endogenous or exogenous)
  7. History of fracture of the humerus, wrist, or vertebra due to fall from standing height or less
  8. History of hip fracture, hip replacement, or non-ambulatory
  9. Long-term use (>6 months) of corticosteroids
  10. History of Parkinson's, HIV, Huntington's disease
  11. History of solid organ transplantation
  12. 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
  13. Severe kidney impairment (eGFR < 30 ml/min),
  14. Active malignancy currently undergoing chemotherapeutic, surgical, or radiation therapy, except non-melanomatous skin cancer
  15. 1-year mortality > 25%, measured by ePrognosis calculator
  16. Planning to move out of the area in the next 12-months
  17. Planning surgery in the next 12-months

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DonepezilDonepezil-
MemantineMemantine-
Primary Outcome Measures
NameTimeMethod
Change in bone mineral density, as measured by dual x-ray absorptiometry (DXA)baseline, 12 months
Secondary Outcome Measures
NameTimeMethod
Change in Trabecular Bone scorebaseline, 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

Duke Memory Disorders Clinic
🇺🇸Durham, North Carolina, United States
Connie Thacker
Contact

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