Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effect of Zoledronic Acid on Patients With Osteoarthritis of the Hip

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04303026
Recruitment Status : Recruiting
First Posted : March 10, 2020
Last Update Posted : March 10, 2020
Sponsor:
Collaborators:
Hormone Laboratory, Aker University Hospital, Oslo, Norway
University of Oslo
Information provided by (Responsible Party):
Mehran Karimzadeh, Martina Hansen's Hospital

Brief Summary:

Hip Osteoarthritis (OA) is one of the most common diseases affecting the ageing population. No specific and safe treatment slowing the development of hip OA as reflected in reduced joint space narrowing has been developed so far. Implantation of hip prosthesis has been a great success, but is expensive and puts a great financial pressure on hospitals and national healthcare programs. It also poses risks of serious complications. Current non-surgical treatment options focus on pain management and physiotherapy.

Bisphosphonates have been shown to exert multiple beneficial effects in OA. Animal studies have demonstrated that bisphosphonates protect against subchondral bone degradation and preserve articular cartilage in mice and rats with OA.

In this study 70 participants will be treated with either Zoledronic Acid (a potent Bisphosphonate) or Placebo (Saltwater). Allocation will be random and both parties are blinded. The investigators hypothesis is that participants treated with Zoledronic acid will have less pain, and better function after 12 months. The results will be tested with functional and pain scores, and functional tests. The study team will also measure the effects on disease related quality of life, bone quality measurements and the effect on bone marrow lesions on MRI (magnetic resonance imaging) and histological examination


Condition or disease Intervention/treatment Phase
Osteoarthritis, Hip Drug: Zoledronic Acid Drug: Saline 0.9% Phase 3

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 70 participants are allocated randomly to either treatment group or placebo group by a member not part of the study group through an internet based website (Studyrandomizer.com) Participants cannot cross over, but they can withdraw from the study or treatment/Placebo or request alternate treatment (surgery)
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: The treatment and placebo is administered through an infusion. Both will be administered in an identical infusion bag and are colorless. The mixing is performed by the same person who randomizes, less than 24 hours before administration. The bags are then put in a refrigerator and picked up later by a study nurse for administration. There is no "personal contact".
Primary Purpose: Treatment
Official Title: A Randomized Placebo Controlled Trial Testing The Effect of Zoledronic Acid on Hip Osteoarthritis
Actual Study Start Date : March 2, 2020
Estimated Primary Completion Date : March 15, 2021
Estimated Study Completion Date : March 15, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Active Comparator: Treatment Group
Participants receiving active treatment with two infusions of Zoledronic Acid 5 mg with 3 months interval mixed in 100 ml 0.9% saline
Drug: Zoledronic Acid
5mg IV infusion
Other Name: Active Treatment

Placebo Comparator: Placebo Group
Participants receiving Placebo with two infusions of 100 ml 0.9% saline with 3 months interval.
Drug: Saline 0.9%
Placebo Group. Saline 0.9% 100 ml infusion
Other Name: Placebo




Primary Outcome Measures :
  1. Mean change in joint pain by VAS (Visual analogue pain scale from 1-10) from baseline to 12 months follow up, in the intervention group compared to the placebo group [ Time Frame: Baseline and 12 months ]
    Pain during weight bearing measured with Visual Analogue Pain Scale


Secondary Outcome Measures :
  1. Mean change in joint pain by VAS from baseline to 3 and 6 months follow up, in the intervention group compared to the placebo group [ Time Frame: baseline, 3 and 6 months ]
    Pain during weight bearing measured with Visual Analogue Pain Scale

  2. Mean change in function and activity score (HOOS) from baseline to 3, 6 and 12 months follow up, in the intervention group compared to the placebo group [ Time Frame: baseline, 3, 6 and 12 months ]
    Function and activity measured with PROM (patient reported outcome measure) Hip Disability and Osteoarthritis, 0-100 worst to best scale

  3. Mean change in function and activity score (HHS) from baseline to 12 months follow up, in the intervention group compared to the placebo group [ Time Frame: 12 months ]
    Function and activity measured with Harris hips score, 0-100 worst to best score.

  4. Mean change in 40mWT (40 meter walking test measured in seconds) from baseline to 3, 6 and 12 months follow up, in intervention group compared to placebo group [ Time Frame: baseline, 3, 6 and 12 months ]
    40 meter walking test measured in seconds

  5. Mean change in SCT (Stair climb test measured in seconds) from baseline to 3, 6 and 12 months follow up, in intervention group compared to placebo group [ Time Frame: baseline, 3, 6 and 12 months ]
    Stair Climb test measured in seconds (11 stairs)

  6. Mean change in 30CST (Chair stand test, measured by number of repetitions in 30 seconds) from baseline to 3, 6 and 12 months follow up, in intervention group compared to placebo group [ Time Frame: baseline, 3, 6 and 12 months ]
    Chair stand test measured in number of repetitions in 30 seconds

  7. Mean change in QoL (EQ-5D) from baseline to 3, 6 and 12 months follow up, in the intervention group compared to the placebo group [ Time Frame: baseline, 3, 6 and 12 months ]
    Use of Euroqol 5 questions (EQ-5D), measuring disease related quality of life. Score is calculated using value set from English population

  8. Change in mean number of doses of Paracetamol, NSAID and/or opiates per week in each group during the last month compared to baseline at 12 months follow up [ Time Frame: baseline, 3, 6 and 12 months ]
    Change in use of pain medication

  9. Number of AE/SAE (adverse events and serious adverse events) and AR/SAR/SUSAR (adverse/serious adverse and suspected unexpected serious adverse reactions) in the intervention group compared to placebo group 12 months after first infusion. [ Time Frame: baseline and 12 months ]
    Registrating number of adverse effects and adverse reactions


Other Outcome Measures:
  1. Change in joint space narrowing (in millimeters) from baseline to 12 months follow up seen on X-ray, compared to the placebo group. [ Time Frame: Baseline and 12 months ]
    exploratory endpoint

  2. Changes in bone turnover in BMLs after treatment with zoledronic acid seen with histomorphometry. A comparison between patients in the treatment and placebo group, that end up with joint implant surgery. [ Time Frame: Baseline and 12 months ]
    Exploratory endpoint. Bone turnover will be assessed after tetracycline double labeling followed by intersection counting of single and double labeled surfaces.

  3. Changes in vascularization in BMLs after treatment with zoledronic acid seen with histomorphometry. A comparison between patients in the treatment and placebo group, that end up with joint implant surgery. [ Time Frame: Baseline and 12 months ]
    Exploratory endpoint. Tissue vascularity will be assessed using point counting.

  4. Changes in bone material properties by impact microindentation (measured in bone material strength index, BMSi) of tibial bone before and after treatment with zoledronic acid compared to the placebo group [ Time Frame: Baseline and 12 months ]
    Exploratory endpoint

  5. Percentage of participants treated with implant surgery of the affected hip in the treatment group compared to placebo group 12 months after the first infusion. [ Time Frame: 12 months ]
    Exploratory endpoint



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 50-80
  • Continuous worsening of hip pain with an onset of minimum 3 months
  • Hip Pain intensity >40mm on a visual analogue scale (VAS) ranging from 0 (no pain) to 100mm (maximal pain) during weight bearing for the last 7 days
  • HHS < 65 (Harris Hip Score)
  • Hip OA fulfilling the ACR (American College of Rheumatology) criteria [33]
  • Hip MRI scan showing large (>1 cm diameter) Bone Marrow lesions (BMLs)
  • Willing and able to consent and comply with the study protocol

Exclusion Criteria:

  • eGFR (estimated glomerular filtration rate) < 35 ml/min or hypocalcemia
  • Exposure to any treatment affecting bone other than Ca+D ( bisphosphonates, Denosumab teriparatide or continuous treatment of prednisolone)
  • Diseases affecting bone and joints (i.e inflammatory joint diseases, osteonecrosis with segmental collapse and deformation, primary bone cancer or known skeletal metastases)
  • Severe vitamin D deficiency (S-25(OH)D < 25 nmol/l) has to be supplemented with Ca+D before zoledronic acid infusion
  • Ipsilateral knee prosthesis
  • Contralateral hip prosthesis
  • Women of child bearing potential (WOCBP). Female participants must be in a postmenopausal state or permanent sterile.
  • Hypersensitivity or previous allergic reaction to ZA or other bisphosphonates.
  • Hypersensitivity or previous allergic reaction to Calcigran Forte (a calcium and vitamine D supplement) or Prednisolone

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04303026


Contacts
Layout table for location contacts
Contact: Mehran Karimzadeh, MD 0047 4143288 mehran.karimzadeh@mhh.no
Contact: Stig Heir, MD, PhD 0047 92250761 stig.heir@mhh.no

Locations
Layout table for location information
Norway
Martina Hansens Hospital Recruiting
Sandvika, Norway
Contact: Kjetil Nerhus, MD, PhD    0047 93409934    kjetil.nerhus@mhh.no   
Sub-Investigator: Pål Borgen, MD, PhD         
Sub-Investigator: Carsten Brocker, MD         
Principal Investigator: Mehran Karimzadeh, MD         
Sub-Investigator: Stig Heir, MD, PhD         
Sub-Investigator: Kjetil Nerhus, MD, PhD         
Sub-Investigator: Lars Nordsletten, MD, PhD         
Sub-Investigator: Erik F Eriksen, MD, PhD         
Sponsors and Collaborators
Martina Hansen's Hospital
Hormone Laboratory, Aker University Hospital, Oslo, Norway
University of Oslo
Investigators
Layout table for investigator information
Study Director: Erik F Eriksen, MD, PhD Helse Sor-Ost
Additional Information:
Publications:

Layout table for additonal information
Responsible Party: Mehran Karimzadeh, Principal investigator, Martina Hansen's Hospital
ClinicalTrials.gov Identifier: NCT04303026    
Other Study ID Numbers: 2018030
2019-000757-31 ( EudraCT Number )
First Posted: March 10, 2020    Key Record Dates
Last Update Posted: March 10, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: No plan has been discussed within the study group yet

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Osteoarthritis
Osteoarthritis, Hip
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Zoledronic Acid
Bone Density Conservation Agents
Physiological Effects of Drugs