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

NCT04303026 | Unknown Phase 3

• 2 other identifiers: 20180302019-000757-31
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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

Conditions

Osteoarthritis, Hip

Outcome Measures

Primary Outcomes (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

  Pain during weight bearing measured with Visual Analogue Pain Scale

  Baseline and 12 months

Secondary Outcomes (9)

• 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

  baseline, 3 and 6 months

• 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

  baseline, 3, 6 and 12 months

• Mean change in function and activity score (HHS) from baseline to 12 months follow up, in the intervention group compared to the placebo group

  12 months

• 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

  baseline, 3, 6 and 12 months

• 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

  baseline, 3, 6 and 12 months

Other Outcomes (6)

• Change in joint space narrowing (in millimeters) from baseline to 12 months follow up seen on X-ray, compared to the placebo group.

  Baseline and 12 months

• 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.

  Baseline and 12 months

• 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.

  Baseline and 12 months

Study Arms (2)

Treatment Group

ACTIVE COMPARATOR

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

Placebo Group

PLACEBO COMPARATOR

Participants receiving Placebo with two infusions of 100 ml 0.9% saline with 3 months interval.

Drug: Saline 0.9%

Interventions

Zoledronic Acid DRUG

5mg IV infusion

Also known as: Active Treatment

Treatment Group

Saline 0.9% DRUG

Placebo Group. Saline 0.9% 100 ml infusion

Also known as: Placebo

Placebo Group

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vestre Viken Hospital Trust: lead
• Hormone Laboratory, Aker University Hospital, Oslo, Norway: collaborator
• University of Oslo: collaborator

Study Sites (1)

Martina Hansens Hospital

Sandvika, Norway

RECRUITING

Related Publications (36)

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Related Links

• Video guide to Osteoarthritis Research Society International (OARSI) Physical tests

MeSH Terms

Conditions

Osteoarthritis, Hip

Interventions

Zoledronic Acid; Sodium Chloride

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Erik F Eriksen, MD, PhD

  Helse Sor-Ost

  STUDY DIRECTOR

Central Study Contacts

Morten H Iversen, MD

CONTACT

0047 40028069; morten.halkjaer.iversen@mhh.no

Stig Heir, MD, PhD

CONTACT

0047 92250761; stig.heir@mhh.no

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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".
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: 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)

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 10, 2020
• Study Start: March 2, 2020
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2024
• Last Updated: October 24, 2022

Record last verified: 2022-10

Locations

NO (1)