lIfestyle iNterventionS for PaIn ReliEf (INSPIRE)

Study Overview
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Brief Summary
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This pilot study will be a placebo controlled randomised intervention study in which participants with knee pain will be grouped into the diet intervention, exercise intervention, diet and exercise intervention or placebo arm. The study involves intake of dietary supplements and performing routine exercises which are commonly used and are not pharmacological agents. The end-points of the study are non-clinical outcomes. N= 120. 2x2 intervention with 30 individuals per block: placebo, diet only, exercise only, diet + exercise

Official Title
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Molecular Signatures of Endocannabinoid Induced Pain Relief in Humans: Lifestyle Interventions, Systemic and Localised Changes

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Dietary Supplement: Inulin Fibre supplement
* Dietary Supplement: Maltodextrin (Placebo)
* Behavioral: Exercise


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 Participant eligibility includes those aged >18 years who have a body mass index (BMI) between 18.5 and 39.9 kg/m2 Exclusion Criteria: The participant may not enter the study if ANY of the following apply: Have psychosocial or gastrointestinal (e.g. malabsorptive conditions such as IBS/IBD, coeliac) Are taking the following medications: immunosuppressants, anticoagulants, amiodarone and/or perhexiline Are currently following or anticipated to commence a specialised commercially available weight loss diet and/or program Pregnant or breast feeding History or current psychiatric illness History or current neurological condition (e.g. epilepsy) Those undergoing revision, having severe hip OA, inflammatory arthropathies Diagnosed non-OA cause of knee pain (e.g. rheumatoid arthritis) Neuropathy or diabetes mellitus Having taken part in a research study in the last 3 months involving invasive procedures or an inconvenience allowance (this must remain for ALL UoN FMHS UREC approved studies)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: 2x2 intervention with 30 individuals per block: placebo, diet only, exercise only, diet + exercise
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo arm<br>The participants in the placebo/control arm (N=30) will be required to take 10g of maltodextrin for the same period of 6 weeks. | Dietary Supplement: Maltodextrin (Placebo)<br>* 10g/ day which can be consumed by adding to breakfast cereal/ smoothie/ yogurt or drink of choice<br>|
| Experimental: Diet only Arm<br>The participants in the dietary intervention arm will be required to take 20g of inulin (N=30) for a period of 6 weeks. | Dietary Supplement: Inulin Fibre supplement<br>* 20g/ day. Inulin is easily dissolvable in liquid and can be incorporated into the usual diet - by adding to water, juice, smoothies, cereal, yogurt etc.<br>|
| Experimental: Exercise only arm<br>Joint Academy An app-based exercises platform (Joint Academy®) will be used as an intervention given to the treatment arm. The programme consists of a mixture of open and close chain exercises, a combination of concentric, eccentric and focusing on the global strength of legs including the muscles around the hips and knee joints as well as balance enhancement exercises. The intervention also includes educational sessions integrated into the programme covering the basics of OA, its treatment, self-managing symptoms of OA and the benefits of maintaining a healthy lifestyle. The exercise intervention focuses on core stability and performance, neuromuscular leg strengthening and balance enhancement. | Behavioral: Exercise<br>* Joint Academy An app-based exercises platform (Joint Academy®) will be used as an intervention given to the treatment arm. The programme consists of a mixture of open and close chain exercises, a combination of concentric, eccentric and focusing on the global strength of legs including the muscles around the hips and knee joints as well as balance enhancement exercises.<br>|
| Experimental: Diet + exercise intervention arm<br>The participants in this arm will be required to take 20g of inulin (N=30) for a period of 6 weeks and doing exercise at the same time. | Dietary Supplement: Inulin Fibre supplement<br>* 20g/ day. Inulin is easily dissolvable in liquid and can be incorporated into the usual diet - by adding to water, juice, smoothies, cereal, yogurt etc.<br>Behavioral: Exercise<br>* Joint Academy An app-based exercises platform (Joint Academy®) will be used as an intervention given to the treatment arm. The programme consists of a mixture of open and close chain exercises, a combination of concentric, eccentric and focusing on the global strength of legs including the muscles around the hips and knee joints as well as balance enhancement exercises.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Numerical Rate Score (NRS) for pain | The Numerical Rate Score (NRS) will be used to assess the changes in the level of pain in response to the intervention between baseline and follow-up. | Baseline and 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum Endocannabinoid levels | Serum levels of Endocannabinoids will be measured using mass spectrometry in samples collected at baseline and at follow-up (at the end of six weeks). This will help us ascertain the change in levels of Endocannabinoids in response to the intervention. | Baseline and 6 weeks | 
| Changes in serum Cytokines levels | Serum levels of cytokines will be measured using ELISA in samples collected at baseline and at follow-up (at the end of six weeks). This will help us ascertain the change in levels of pro and anti-inflammatory cytokines in response to the intervention. | Baseline and 6 weeks | 
| Changes in serum markers of immune phenotyping (PBMCs) | Serum levels of PBMCs will be measured using a multiplex technique in samples collected at baseline and at follow-up (at the end of six weeks). This will help us ascertain the change in immunological function in response to the intervention. | Baseline and 6 weeks | 
| Changes in gut microbiome composition and short chain fatty acids | Changes in gut microbiome composition and serum levels of short-chain fatty acids (SCFAs) in response to the interventions. Gut microbiome composition will be measured using 16S sequencing on stool samples. SCFAs in serum will be measured using mass spectrometry. | Baseline and 6 weeks | 
| Changes in DNA methylation on a subset of individuals | DNA methylation will be measured using specialized ELISA kits in samples collected at baseline and at follow-up (at the end of six weeks). | Baseline and 6 weeks |