Alendronate for Hip Osteonecrosis in Adults With Sickle Cell Disease

Study Overview
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Brief Summary
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A prospective, single-arm, intervention study of oral alendronate in adults with sickle cell disease and hip osteonecrosis

Detailed Description
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The investigators hypothesize that adults with sickle cell disease (SCD) and osteonecrosis of the femoral head (ONFH) will tolerate oral alendronate 70 mg administered once a week for 24 weeks (6 months). In addition to collecting safety and tolerability data on alendronate in study participants, the investigators will also measure the preliminary efficacy of alendronate using changes in the Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) Pain Impact scores from baseline to 3-months and 6-months after alendronate initiation. Serum and urine specimen will also be collected to assess changes in bone biomarkers at baseline, 3-months, and 6-months. The investigators plan to recruit 24 adults with SCD from the University of California Davis Medical Center to this single-arm, open label, interventional study. The investigators anticipate enrolling 1-2 participants per month between Sep 2023- Dec 2024. The study endpoints are summarized below: To determine the recruitment and retention rates of adults with SCD-related ONFH enrolled in this prospective, single-arm, open label alendronate interventional study To measure the safety, tolerability, and preliminary efficacy of oral alendronate in adults with SCD-related ONFH over a 6-month treatment duration To measure changes in bone biomarkers in the serum and urine of study participants not receiving chronic red blood cell transfusions at 3 time points: baseline, 3-months, and 6-months after initiation of alendronate The investigators' goal is to complete primary data analysis by May 2025.

Official Title
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A Feasibility Study of Alendronate as Treatment for Femoral Head Osteonecrosis in Adults With Sickle Cell Disease

Conditions
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Sickle Cell Disease, Sickle Cell Anemia, Osteonecrosis, Ischemic Necrosis, Avascular Necrosis

Intervention / Treatment
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* Drug: Alendronate Sodium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years with SCD (any genotype, confirmed by hemoglobin electrophoresis or high performance liquid chromatography) Ability to provide written informed consent Ability to lay on a dual-energy X-ray absorptiometry (DXA) scanner Negative urine pregnancy test for anyone of childbearing potential at study entry Exclusion Criteria: Pregnant women Adults unable to consent Individuals who are not yet adults (infants, children, teenagers) Prisoners Hospitalizations (for any cause) within 2 weeks of study entry

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective cohort of 24 adults with sickle cell disease and hip osteonecrosis
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alendronate group<br>Single-arm prospective cohort of 24 adult with SCD | Drug: Alendronate Sodium<br>* Administer oral alendronate 70 mg once a week x 24 weeks to all study participants<br>* Other names: Binosto;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment and retention rates | Proportion of eligible patients who get recruited to the study; number of enrolled patients who complete 6-month study | up to 28 weeks | 
| Incidence of Treatment-Emergent Adverse Events as assessed by participant report | Collect all adverse events reported by patients and determine if related to study drug | up to 28 weeks | 
| Pain assessed by the Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) Pain Impact questionnaire | The Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) Pain Impact questionnaire is a patient-reported outcome measure of pain level in the past 7 days. The ASCQ-Me pain scale ranges from 0-100, with a standardized mean of 50 and a standard deviation of 10, where lower scores signify worse disease impact. | up to 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum CTX-1 | Measurement of C-terminal telopeptide of type I collagen (CTX) in serum as a biomarker for osteoclast activity (bone resorption) | baseline, 3 months, 6 months | 
| Serum P1NP | Measurement of Procollagen type I N-terminal propeptide (P1NP) in serum as a biomarker for osteoblast activity (bone formation) | baseline, 3 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sickle cell disease, sickle cell anemia, osteonecrosis of the femoral head, hip osteonecrosis, ischemic necrosis of the femur, avascular necrosis of the femur