Do Nanobubbles Improve Joint Hypoxia?

Study Overview
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Brief Summary
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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.

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

Conditions
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Rheumatoid Arthritis, Psoriatic Arthritis

Intervention / Treatment
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* Dietary Supplement: Nanobubble drink


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nanobubble<br>Sports drink nanobubble drink | Dietary Supplement: Nanobubble drink<br>* Commercially available sports drink<br>|
| Placebo Comparator: control<br>Flavoured drink- no active ingredients | Dietary Supplement: Nanobubble drink<br>* Commercially available sports drink<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |