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Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention Following an Acute Knee Injury (ZAPOA)

Primary Purpose

Anterior Cruciate Ligament Tear, Anterior Cruciate Ligament Rupture, Anterior Cruciate Ligament Injuries

Status
Recruiting
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Zoledronic Acid Injection
Placebo
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anterior Cruciate Ligament Tear focused on measuring acl tear, acl, acl rupture, acl injury, osteo arthritis

Eligibility Criteria

25 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Clinical evidence of an acute unilateral ACL tear (full-thickness, complete tear) will be recruited. This age range is chosen to ensure participants have fully developed adult bone structures and to exclude participants with menopause as this could affect study results.
  • Participants with combined ligament deficiencies (posterior cruciate, medial and/or lateral collateral) or meniscal injury will be included. Participants must be able to fully extend the knee while supported at the time of the baseline measurement in order to conduct the HR-pQCT scan.
  • Participants with a serum calcium level in the normal range (2.1-2.55 mmol/L) and a creatinine level above 50 (reported as eGFR) will be included.

Exclusion Criteria:

  • Individuals with contraindications to zoledronic acid (see below)
  • Prior knee ligament and/or meniscus tears, and/or intra-articular fractures.
  • Females who are pregnant or planning pregnancy within a year will not be eligible. The research team will recommend participants who are planning to become pregnant within the next five years to withdraw their participation.
  • Individuals with knees larger than the CT scanner's circular field of view.
  • Individuals with a history of disease and/or treatment affecting bone turnover in the past 12 months.
  • Individuals with injuries or implants that are not MRI-safe.

Zoledronic acid is contraindicated for:

  • Patients who are hypersensitive to this drug or to any ingredient in the formulation, or to any bisphosphonates or component of the container.
  • Severe renal impairment with creatinine clearance <35 mL/min and in those with evidence of acute renal impairment. For this study, participants with a creatinine clearance <50 mL/min may be excluded.
  • Non-corrected hypocalcaemia at the time of infusion.
  • Pregnant and nursing mothers.
  • Patients who are already taking another bisphosphonate (ex. for osteoporosis).

Sites / Locations

  • University of CalgaryRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Zoledronic Acid Injection

Placebo

Arm Description

Participants will receive 1 dose of 5 mg/100 mL intravenous zoledronic acid

Participants will receive 1 dose 100 ml Saline.

Outcomes

Primary Outcome Measures

Bone microarchitecture changes at 6 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
To determine morphological parameters from HR-pQCT scans, the trabecular portion must be isolated from the cortical shell of the bone in order to analyse the components separately. This is accomplished with an already developed auto-segmentation algorithm. In addition, the raw HR-pQCT images must be converted to binary images, wherein each voxel (3D pixel) is either labelled 'bone' or 'not bone.' This segmentation is performed by an algorithm which applies either a Gaussian or Laplace-Hamming filter in addition to a threshold to the grey-scale images. The binary images can then be analysed and morphological parameters can be determined. The changes in bone microarchitecture will be assessed at 6 months in comparison to baseline.
Bone microarchitecture changes at 18 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
To determine morphological parameters from HR-pQCT scans, the trabecular portion must be isolated from the cortical shell of the bone in order to analyse the components separately. This is accomplished with an already developed auto-segmentation algorithm. In addition, the raw HR-pQCT images must be converted to binary images, wherein each voxel (3D pixel) is either labelled 'bone' or 'not bone.' This segmentation is performed by an algorithm which applies either a Gaussian or Laplace-Hamming filter in addition to a threshold to the grey-scale images. The binary images can then be analysed and morphological parameters can be determined. The changes in bone microarchitecture will be assessed at 18 months in comparison to baseline.

Secondary Outcome Measures

Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
MRI data will be segmented to identify the bone surface in a similar fashion as described for the HR-pQCT data. Subsequently, using a threshold based approach BMLs will be identified and their locations and volumes will be recorded. Next, using rigid body registration the MRI data will be transformed to the HR-pQCT data. That allows the analysis of bone microarchitecture exclusively within the volume of BMLs. All of these analysis steps will be performed using custom algorithms in Python and the visualization toolkit. The changes in bone will be assessed at 2 months comparison to baseline.
Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
MRI data will be segmented to identify the bone surface in a similar fashion as described for the HR-pQCT data. Subsequently, using a threshold based approach BMLs will be identified and their locations and volumes will be recorded. Next, using rigid body registration the MRI data will be transformed to the HR-pQCT data. That allows the analysis of bone microarchitecture exclusively within the volume of BMLs. All of these analysis steps will be performed using custom algorithms in Python and the visualization toolkit. The changes in bone will be assessed at 6 months in comparison to baseline.
Knee alignment as assessed by bi-planar x-ray
Joint alignment by bi-planar x-ray (EOS) In a standing position, the baseline study visit will capture the alignment of the tibia and femur bones bilaterally so that alignment of the knee joint can be assessed. This is a standard clinical imaging device, and the software for measurement of knee alignment is built into the system.
Patient reported outcomes using ACL Quality of Life Questionnaire - Baseline
Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Patient reported outcomes using ACL Quality of Life Questionnaire - 2 Months
Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Patient reported outcomes using ACL Quality of Life Questionnaire - 6 Months
Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Patient reported outcomes using ACL Quality of Life Questionnaire - 18 Months
Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) - Questionnaire - Baseline
Patient reported outcomes will be assessed using - Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 2 Months
Patient reported outcomes will be assessed using - Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 6 Months
Patient reported outcomes will be assessed using - Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 18 Months
Patient reported outcomes will be assessed using - Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - Baseline
Patient reported outcomes will be assessed using - 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 2 months
Patient reported outcomes will be assessed using - 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 6 months
Patient reported outcomes will be assessed using - 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 18 months
Patient reported outcomes will be assessed using - 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Patient reported outcomes using EQ-5D-5L Questionnaire - Baseline
Patient reported outcomes will be assessed using - EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Patient reported outcomes using EQ-5D-5L Questionnaire - 2 months
Patient reported outcomes will be assessed using - EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Patient reported outcomes using EQ-5D-5L Questionnaire - 6 months
Patient reported outcomes will be assessed using - EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Patient reported outcomes using EQ-5D-5L Questionnaire - 18 months
Patient reported outcomes will be assessed using - EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Patient reported outcomes Health History Questionnaire (HHQ) - Baseline
Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale)
Patient reported outcomes Health History Questionnaire (HHQ) - 2 months
Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale)
Patient reported outcomes Health History Questionnaire (HHQ) - 6 months
Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale)
Patient reported outcomes Health History Questionnaire (HHQ) - 18 months
Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale)

Full Information

First Posted
December 21, 2021
Last Updated
May 16, 2023
Sponsor
University of Calgary
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1. Study Identification

Unique Protocol Identification Number
NCT05204836
Brief Title
Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention Following an Acute Knee Injury
Acronym
ZAPOA
Official Title
Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 16, 2023 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Calgary

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to assess if a zoledronic acid injection can alter the trajectory of joint degeneration following an acute anterior cruciate ligament (ACL) injury.
Detailed Description
After being informed about the study and potential risks and all participants giving written informed consent, this project will establish a cohort of young men and women who within six weeks have sustained an acute rupture of the ACL. The cohort is randomized into a control and treatment group, where the treatment group receives a zoledronic acid injection at baseline. The cohort will be followed radiographically with high resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy computed tomography (DECT), digital radiography (X-Ray), bi-planar X-ray (EOS) and magnetic resonance imaging (MRI) for eighteen months to monitor the progression of joint changes and the effects of zoledronic acid.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anterior Cruciate Ligament Tear, Anterior Cruciate Ligament Rupture, Anterior Cruciate Ligament Injuries, Osteo Arthritis Knee
Keywords
acl tear, acl, acl rupture, acl injury, osteo arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
The cohort is randomized into a control and treatment group, where the treatment group receives a zoledronic acid injection within 6 weeks of ACL injury.
Masking
Participant
Allocation
Randomized
Enrollment
56 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Zoledronic Acid Injection
Arm Type
Experimental
Arm Description
Participants will receive 1 dose of 5 mg/100 mL intravenous zoledronic acid
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive 1 dose 100 ml Saline.
Intervention Type
Drug
Intervention Name(s)
Zoledronic Acid Injection
Other Intervention Name(s)
Taro-Zoledronic Acid, Dr. Reddy's Zoledronic Acid Injection
Intervention Description
5 mg / 100 mL intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline
Intervention Description
100 mL intravenous infusion
Primary Outcome Measure Information:
Title
Bone microarchitecture changes at 6 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
Description
To determine morphological parameters from HR-pQCT scans, the trabecular portion must be isolated from the cortical shell of the bone in order to analyse the components separately. This is accomplished with an already developed auto-segmentation algorithm. In addition, the raw HR-pQCT images must be converted to binary images, wherein each voxel (3D pixel) is either labelled 'bone' or 'not bone.' This segmentation is performed by an algorithm which applies either a Gaussian or Laplace-Hamming filter in addition to a threshold to the grey-scale images. The binary images can then be analysed and morphological parameters can be determined. The changes in bone microarchitecture will be assessed at 6 months in comparison to baseline.
Time Frame
Baseline, 6 months
Title
Bone microarchitecture changes at 18 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
Description
To determine morphological parameters from HR-pQCT scans, the trabecular portion must be isolated from the cortical shell of the bone in order to analyse the components separately. This is accomplished with an already developed auto-segmentation algorithm. In addition, the raw HR-pQCT images must be converted to binary images, wherein each voxel (3D pixel) is either labelled 'bone' or 'not bone.' This segmentation is performed by an algorithm which applies either a Gaussian or Laplace-Hamming filter in addition to a threshold to the grey-scale images. The binary images can then be analysed and morphological parameters can be determined. The changes in bone microarchitecture will be assessed at 18 months in comparison to baseline.
Time Frame
Baseline, 18 months
Secondary Outcome Measure Information:
Title
Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
Description
MRI data will be segmented to identify the bone surface in a similar fashion as described for the HR-pQCT data. Subsequently, using a threshold based approach BMLs will be identified and their locations and volumes will be recorded. Next, using rigid body registration the MRI data will be transformed to the HR-pQCT data. That allows the analysis of bone microarchitecture exclusively within the volume of BMLs. All of these analysis steps will be performed using custom algorithms in Python and the visualization toolkit. The changes in bone will be assessed at 2 months comparison to baseline.
Time Frame
Baseline, 2 months
Title
Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
Description
MRI data will be segmented to identify the bone surface in a similar fashion as described for the HR-pQCT data. Subsequently, using a threshold based approach BMLs will be identified and their locations and volumes will be recorded. Next, using rigid body registration the MRI data will be transformed to the HR-pQCT data. That allows the analysis of bone microarchitecture exclusively within the volume of BMLs. All of these analysis steps will be performed using custom algorithms in Python and the visualization toolkit. The changes in bone will be assessed at 6 months in comparison to baseline.
Time Frame
Baseline, 6 months
Title
Knee alignment as assessed by bi-planar x-ray
Description
Joint alignment by bi-planar x-ray (EOS) In a standing position, the baseline study visit will capture the alignment of the tibia and femur bones bilaterally so that alignment of the knee joint can be assessed. This is a standard clinical imaging device, and the software for measurement of knee alignment is built into the system.
Time Frame
Baseline
Title
Patient reported outcomes using ACL Quality of Life Questionnaire - Baseline
Description
Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Time Frame
Baseline
Title
Patient reported outcomes using ACL Quality of Life Questionnaire - 2 Months
Description
Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Time Frame
2 Months
Title
Patient reported outcomes using ACL Quality of Life Questionnaire - 6 Months
Description
Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Time Frame
6 Months
Title
Patient reported outcomes using ACL Quality of Life Questionnaire - 18 Months
Description
Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Time Frame
18 Months
Title
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) - Questionnaire - Baseline
Description
Patient reported outcomes will be assessed using - Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Time Frame
Baseline
Title
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 2 Months
Description
Patient reported outcomes will be assessed using - Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Time Frame
2 months
Title
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 6 Months
Description
Patient reported outcomes will be assessed using - Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Time Frame
6 months
Title
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 18 Months
Description
Patient reported outcomes will be assessed using - Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Time Frame
18 months
Title
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - Baseline
Description
Patient reported outcomes will be assessed using - 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Time Frame
Baseline
Title
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 2 months
Description
Patient reported outcomes will be assessed using - 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Time Frame
2 months
Title
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 6 months
Description
Patient reported outcomes will be assessed using - 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Time Frame
6 months
Title
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 18 months
Description
Patient reported outcomes will be assessed using - 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Time Frame
18 months
Title
Patient reported outcomes using EQ-5D-5L Questionnaire - Baseline
Description
Patient reported outcomes will be assessed using - EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Time Frame
Baseline
Title
Patient reported outcomes using EQ-5D-5L Questionnaire - 2 months
Description
Patient reported outcomes will be assessed using - EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Time Frame
2 months
Title
Patient reported outcomes using EQ-5D-5L Questionnaire - 6 months
Description
Patient reported outcomes will be assessed using - EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Time Frame
6 months
Title
Patient reported outcomes using EQ-5D-5L Questionnaire - 18 months
Description
Patient reported outcomes will be assessed using - EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Time Frame
18 months
Title
Patient reported outcomes Health History Questionnaire (HHQ) - Baseline
Description
Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale)
Time Frame
Baseline
Title
Patient reported outcomes Health History Questionnaire (HHQ) - 2 months
Description
Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale)
Time Frame
2 months
Title
Patient reported outcomes Health History Questionnaire (HHQ) - 6 months
Description
Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale)
Time Frame
6 months
Title
Patient reported outcomes Health History Questionnaire (HHQ) - 18 months
Description
Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale)
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Clinical evidence of an acute unilateral ACL tear (full-thickness, complete tear) will be recruited. This age range is chosen to ensure participants have fully developed adult bone structures and to exclude participants with menopause as this could affect study results. Participants with combined ligament deficiencies (posterior cruciate, medial and/or lateral collateral) or meniscal injury will be included. Participants must be able to fully extend the knee while supported at the time of the baseline measurement in order to conduct the HR-pQCT scan. Participants with a serum calcium level in the normal range (2.1-2.55 mmol/L) and a creatinine level above 50 (reported as eGFR) will be included. Exclusion Criteria: Individuals with contraindications to zoledronic acid (see below) Prior knee ligament and/or meniscus tears, and/or intra-articular fractures. Females who are pregnant or planning pregnancy within a year will not be eligible. The research team will recommend participants who are planning to become pregnant within the next five years to withdraw their participation. Individuals with knees larger than the CT scanner's circular field of view. Individuals with a history of disease and/or treatment affecting bone turnover in the past 12 months. Individuals with injuries or implants that are not MRI-safe. Zoledronic acid is contraindicated for: Patients who are hypersensitive to this drug or to any ingredient in the formulation, or to any bisphosphonates or component of the container. Severe renal impairment with creatinine clearance <35 mL/min and in those with evidence of acute renal impairment. For this study, participants with a creatinine clearance <50 mL/min may be excluded. Non-corrected hypocalcaemia at the time of infusion. Pregnant and nursing mothers. Patients who are already taking another bisphosphonate (ex. for osteoporosis).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Steven Boyd, PhD
Phone
4032203664
Email
skboyd@ucalgary.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Boyd, PhD
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gregory Kline, MD
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 1N4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steven Boyd, PhD
Phone
4032203664
Email
skboyd@ucalgary.ca
First Name & Middle Initial & Last Name & Degree
Steven Boyd, PhD
First Name & Middle Initial & Last Name & Degree
Gregory Kline, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
25182676
Citation
Dare D, Rodeo S. Mechanisms of post-traumatic osteoarthritis after ACL injury. Curr Rheumatol Rep. 2014 Oct;16(10):448. doi: 10.1007/s11926-014-0448-1.
Results Reference
background
PubMed Identifier
17761605
Citation
Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007 Oct;35(10):1756-69. doi: 10.1177/0363546507307396. Epub 2007 Aug 29.
Results Reference
background
PubMed Identifier
7391091
Citation
Noyes FR, Bassett RW, Grood ES, Butler DL. Arthroscopy in acute traumatic hemarthrosis of the knee. Incidence of anterior cruciate tears and other injuries. J Bone Joint Surg Am. 1980 Jul;62(5):687-95, 757.
Results Reference
background
PubMed Identifier
1415878
Citation
Speer KP, Spritzer CE, Bassett FH 3rd, Feagin JA Jr, Garrett WE Jr. Osseous injury associated with acute tears of the anterior cruciate ligament. Am J Sports Med. 1992 Jul-Aug;20(4):382-9. doi: 10.1177/036354659202000403.
Results Reference
background
PubMed Identifier
8368416
Citation
Spindler KP, Schils JP, Bergfeld JA, Andrish JT, Weiker GG, Anderson TE, Piraino DW, Richmond BJ, Medendorp SV. Prospective study of osseous, articular, and meniscal lesions in recent anterior cruciate ligament tears by magnetic resonance imaging and arthroscopy. Am J Sports Med. 1993 Jul-Aug;21(4):551-7. doi: 10.1177/036354659302100412.
Results Reference
background
PubMed Identifier
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Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention Following an Acute Knee Injury

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