Do Nanobubbles Improve Joint Hypoxia?

An Investigation of Whether Orally Delivered Nanobubbles Have a Physiological Effect on Joint Hypoxia?

Inflamed joints in patients with rheumatoid arthritis and psoriatic arthritis are characterized by low oxygen levels and inflammation. We propose to investigate whether tiny bubbles (nanobubbles) when given in a drink can alter oxygen level in joints. These nanobubbles are so small that they can enter the bloodstream when given as a drink. This information will give new information on the role of oxygen in joint inflammation and could possibly lead to new treatment approaches in the future.

Study Overview

• Status: Withdrawn
• Conditions: Rheumatoid Arthritis; Psoriatic Arthritis
• Intervention / Treatment: Dietary supplement: Nanobubble drink

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Oxford, United Kingdom, OX3 7LD
    • Oxford University Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Participant is willing and able to give informed consent for participation in the study.

  • Male or Female, aged 18 years or above.
  • Fulfil American College of Rheumatology/European League Against Rheumatism criteria (ACR/EULAR) 2010 Rheumatoid Arthritis Classification Criteria or fulfil Classification Criteria for Psoriatic Arthritis 2006 (CASPAR).
  • Selected joint for biopsy must be minimum Grade 2 synovial thickening for large joint (knee) and medium joint (wrist), or minimum Grade 3 synovial thickening for small joint (metacarpophalangeal).
  • Women of child bearing potential who are willing to use effective contraception (i.e. barrier, oral contraceptive pill, implanted contraception, or previous hysterectomy, bilateral oophorectomy) for the duration of the study.

Exclusion Criteria:

• • Currently on oxygen therapy.

  • Current enrolment in any other clinical study involving an investigational study treatment.
  • Pregnant or lactating, or women planning to become pregnant or initiating breastfeeding.
  • Intramuscular, intravenous or intra-articular administration of corticosteroid within 4 weeks prior to baseline visit.
  • Oral corticosteroid > 10 mg/day prednisolone or equivalent within 4 weeks prior to baseline visit.
  • Oral corticosteroid dose not stable for at least 4 weeks prior to baseline visit.
  • Oral non-steroidal anti-inflammatory drugs (including aspirin > 75 mg/ day and selective-cyclooxygenase inhibitors) dose not stable for at least 4 weeks prior to baseline visit.
  • Disease modifying anti-rheumatic drugs (DMARDs) dose not stable for at least 4 weeks prior to baseline visit.
  • History of septic arthritis.
  • Participants on warfarin, heparin, low molecular weight heparin, direct oral anticoagulants. Oral anti-platelet agents are permitted.
  • History of haemophilia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nanobubble; Sports drink nanobubble drink	Dietary supplement: Nanobubble drink; Commercially available sports drink
Placebo Comparator: control; Flavoured drink- no active ingredients	Dietary supplement: Nanobubble drink; Commercially available sports drink

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Synovial fluid pO2	Change in synovial fluid pO2 between day 1 and day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hypoxia-inducible factor 1α (HIF-1α) protein levels in synovial tissues		Change in hypoxia-inducible factor 1α (HIF-1α) protein between day 1 and day 28
Treatment Satisfaction Questionnaire for Medication (C)	Validated PRO assessing: side effects, effectiveness, convenience and global satisfaction	Day28

Other Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the absolute and relative cell count in synovial fluid and synovial biopsy	day 28
Change from baseline of synovial fibroblast protein expression	day 28

Collaborators and Investigators

• Sponsor: University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Actual): May 17, 2022
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: March 30, 2021
• First Submitted That Met QC Criteria: April 12, 2021
• First Posted (Actual): April 14, 2021

Study Record Updates

• Last Update Posted (Actual): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Signs and Symptoms, Respiratory; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Hypoxia
• Other Study ID Numbers: PID 15065

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No