Trial Outcomes & Findings for lIfestyle iNterventionS for PaIn ReliEf (INSPIRE) (NCT NCT05670314)

NCT ID: NCT05670314

Last Updated: 2025-09-16

Results Overview

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. Participants reported their pain on a scale ranging from 0 to 10, where 0 represents no pain and 10 the worst pain imaginable.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 117 participants
• Primary outcome timeframe: Baseline and 6 weeks
• Results posted on: 2025-09-16

Participant Flow

Participant milestones

Measure	Placebo Arm The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.	Diet Only Arm The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm 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.	Diet + Exercise Intervention Arm The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.
Overall Study STARTED	27	26	40	24
Overall Study COMPLETED	27	26	40	24
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Placebo Arm n=27 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.	Diet Only Arm n=26 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=40 Participants 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.	Diet + Exercise Intervention Arm n=24 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Total n=117 Participants Total of all reporting groups
Age, Continuous	69.59 Years STANDARD_DEVIATION 6.41 • n=27 Participants	66.54 Years STANDARD_DEVIATION 11.39 • n=26 Participants	67.75 Years STANDARD_DEVIATION 10.22 • n=40 Participants	66.71 Years STANDARD_DEVIATION 8.44 • n=24 Participants	67.69 Years STANDARD_DEVIATION 9.48 • n=117 Participants
Sex: Female, Male Female	14 Participants n=27 Participants	14 Participants n=26 Participants	26 Participants n=40 Participants	14 Participants n=24 Participants	68 Participants n=117 Participants
Sex: Female, Male Male	13 Participants n=27 Participants	12 Participants n=26 Participants	14 Participants n=40 Participants	10 Participants n=24 Participants	49 Participants n=117 Participants
Race and Ethnicity Not Collected	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Body mass index	29.60 kg/m2 STANDARD_DEVIATION 4.65 • n=27 Participants	30.15 kg/m2 STANDARD_DEVIATION 3.75 • n=26 Participants	29.00 kg/m2 STANDARD_DEVIATION 7.15 • n=40 Participants	29.60 kg/m2 STANDARD_DEVIATION 4.65 • n=24 Participants	29.48 kg/m2 STANDARD_DEVIATION 5.32 • n=117 Participants
Pain Numerical Rating Scale	3.52 units on a scale STANDARD_DEVIATION 2.77 • n=27 Participants	4.06 units on a scale STANDARD_DEVIATION 2.85 • n=26 Participants	4.21 units on a scale STANDARD_DEVIATION 2.88 • n=40 Participants	3.92 units on a scale STANDARD_DEVIATION 1.75 • n=24 Participants	3.96 units on a scale STANDARD_DEVIATION 2.67 • n=117 Participants

PRIMARY outcome

Timeframe: Baseline and 6 weeks

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.

Participants reported their pain on a scale ranging from 0 to 10, where 0 represents no pain and 10 the worst pain imaginable.

Outcome measures

Measure	Diet Only Arm n=26 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=40 Participants 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.	Diet + Exercise Intervention Arm n=24 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=27 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Numerical Rate Score (NRS) for Pain	-0.73 units on a scale Standard Deviation 2.32	-1.25 units on a scale Standard Deviation 2.69	-1.21 units on a scale Standard Deviation 1.76	0.67 units on a scale Standard Deviation 2.49

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Measures how many times a participant can rise from a chair to a full standing position in 30 seconds.

Outcome measures

Measure	Diet Only Arm n=26 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=40 Participants 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.	Diet + Exercise Intervention Arm n=24 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=27 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Functional Outcome 30-seconds Sit-to-stand (30CST)	2.12 stands Standard Deviation 3.02	2.54 stands Standard Deviation 3.38	3.21 stands Standard Deviation 5.37	1.23 stands Standard Deviation 1.67

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Time in seconds to stand up, walk 3m, return, and sit. Average of 3 trials at baseline and follow-up (at the end of 6 weeks).

Outcome measures

Measure	Diet Only Arm n=26 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=40 Participants 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.	Diet + Exercise Intervention Arm n=24 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=27 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Functional Outcome Timed-up and go (TUG)	-1.19 seconds Standard Deviation 2.19	-2.07 seconds Standard Deviation 5.82	-0.78 seconds Standard Deviation 1.14	-0.43 seconds Standard Deviation 1.06

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Measured with dynamometer; average of 3 trials on dominant hand in seated position with participant applying as much grip pressure as possible on the dynamometer. The maximum reading (kg) in taken for each repetition.

Outcome measures

Measure	Diet Only Arm n=26 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=40 Participants 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.	Diet + Exercise Intervention Arm n=24 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=27 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Functional Outcome Grip Strength	0.76 kg Standard Deviation 3.42	0.02 kg Standard Deviation 5.62	0.76 kg Standard Deviation 3.42	-1.43 kg Standard Deviation 6.44

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Pain sensitisation will be measured using quantitative sensory testing (QST) to assess any changes in pain sensitisation indices from at baseline to follow-up. QST is a non-invasive method to assess pain sensitivity using standardised stimuli like mechanical pressure or sharpness. We used the QST modality temporal summation (TS). TS assesses sensitivity to sharpness by applying a brief "pinprick" stimulus (256 mN Pinprick; MRC-Systems, Heidelberg, Germany) to the skin with higher ratings potentially suggesting increased spinal cord pain sensitivity. A single stimulus was applied to the rectus femoris (5cm above the mid-point of the patella of the most painful knee), followed by 10 repetitive stimuli at 1/s. Participants rated pain/sharpness intensity on a 0-10 Visual Analogue Scale after both the single and the average of the repeated stimuli. Each test was performed twice, with a 2-minute break between repetitions and the average was taken.

Outcome measures

Measure	Diet Only Arm n=26 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=40 Participants 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.	Diet + Exercise Intervention Arm n=24 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=27 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Pain Sensitisation Outcome Temporal Summation (TS)	-0.20 units on a scale Standard Deviation 1.52	-0.17 units on a scale Standard Deviation 1.62	-0.63 units on a scale Standard Deviation 2.01	0.30 units on a scale Standard Deviation 1.66

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Pain sensitisation will be measured using quantitative sensory testing (QST) to assess any changes in pain sensitisation indices from at baseline to follow-up. QST is a non-invasive method to assess pain sensitivity using standardised stimuli like mechanical pressure or sharpness. We used the QST modality pressure pain detection threshold (PPT) at anatomical position: quadricep (2cm above superolateral edge of patella). PPT measures the lowest pressure a participant perceives as painful while pressure is applied using a handheld probe (Medoc-AlgoMed, Israel) at a rate of 50 kPa/s on the most painful knee, with lower PPT threshold suggestive of increased pain sensitivity.

Outcome measures

Measure	Diet Only Arm n=26 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=40 Participants 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.	Diet + Exercise Intervention Arm n=24 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=27 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Changes in Pain Sensitisation Outcome Pressure Pain Detection Threshold (PPT) at the Superolateral Patella Site	-29.89 kPa Standard Deviation 175.35	-92.74 kPa Standard Deviation 159.03	-39.22 kPa Standard Deviation 240.27	-87.19 kPa Standard Deviation 103.53

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Pain sensitisation will be measured using quantitative sensory testing (QST) to assess any changes in pain sensitisation indices from at baseline to follow-up. QST is a non-invasive method to assess pain sensitivity using standardised stimuli like mechanical pressure or sharpness. We used the QST modality pressure pain detection threshold (PPT) at anatomical position: quadricep (2cm above superomedial edge of patella). PPT measures the lowest pressure a participant perceives as painful while pressure is applied using a handheld probe (Medoc-AlgoMed, Israel) at a rate of 50 kPa/s on the most painful knee, with lower PPT threshold suggestive of increased pain sensitivity.

Outcome measures

Measure	Diet Only Arm n=26 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=40 Participants 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.	Diet + Exercise Intervention Arm n=24 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=27 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Changes in Pain Sensitisation Outcome Pressure Pain Detection Threshold (PPT) at the Superomedial Patella Site	-25.33 kPa Standard Deviation 122.58	-41.25 kPa Standard Deviation 126.96	-22.28 kPa Standard Deviation 131.10	-46.73 kPa Standard Deviation 137.77

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Pain sensitisation will be measured using quantitative sensory testing (QST) to assess any changes in pain sensitisation indices from abeline to follow-up. QST is a non-invasive method to assess pain sensitivity using standardised stimuli like mechanical pressure or sharpness. We used the QST modality pressure pain detection threshold (PPT) at the anatomical position: medial joint line (3cm medially from medial edge of patella). PPT measures the lowest pressure a participant perceives as painful while pressure is applied using a handheld probe (Medoc-AlgoMed, Israel) at a rate of 50 kPa/s on the most painful knee, with lower PPT threshold suggestive of increased pain sensitivity.

Outcome measures

Measure	Diet Only Arm n=26 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=40 Participants 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.	Diet + Exercise Intervention Arm n=24 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=27 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Changes in Pain Sensitisation Outcome Pressure Pain Detection Threshold (PPT) at the Medial Joint Line Site	-31.72 kPa Standard Deviation 132.51	-10.91 kPa Standard Deviation 149.56	-24.02 kPa Standard Deviation 160.48	-54.54 kPa Standard Deviation 132.90

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Pain sensitisation will be measured using quantitative sensory testing (QST) to assess any changes in pain sensitisation indices from at baseline to follow-up. QST is a non-invasive method to assess pain sensitivity using standardised stimuli like mechanical pressure or sharpness. We used the QST modality pressure pain detection threshold (PPT) at anatomical position: tibialis anterior (5 cm distal and 1 cm lateral to the tibial tuberosity). PPT measures the lowest pressure a participant perceives as painful while pressure is applied using a handheld probe (Medoc-AlgoMed, Israel) at a rate of 50 kPa/s on the most painful knee, with lower PPT threshold suggestive of increased pain sensitivity.

Outcome measures

Measure	Diet Only Arm n=26 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=40 Participants 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.	Diet + Exercise Intervention Arm n=24 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=27 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Changes in Pain Sensitisation Outcome Pressure Pain Detection Threshold (PPT) at the Tibialis Anterior Muscle Site	-17.57 kPa Standard Deviation 161.22	-7.74 kPa Standard Deviation 122.59	-20.66 kPa Standard Deviation 180.73	-47.36 kPa Standard Deviation 160.31

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Pain sensitisation will be measured using quantitative sensory testing (QST) to assess any changes in pain sensitisation indices from baseline to follow-up. QST is a non-invasive method to assess pain sensitivity using standardised stimuli like mechanical pressure or sharpness. We used the QST modality pressure pain detection threshold (PPT) at anatomical position: brachioradialis (5 cm medial and distal to the lateral epicondyle) on the arm opposite the painful knee. PPT measures the lowest pressure a participant perceives as painful while pressure is applied using a handheld probe (Medoc-AlgoMed, Israel) at a rate of 50 kPa/s on the arm opposite the painful knee, with lower PPT threshold suggestive of increased pain sensitivity.

Outcome measures

Measure	Diet Only Arm n=26 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=40 Participants 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.	Diet + Exercise Intervention Arm n=24 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=27 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Changes in Pain Sensitisation Outcome Pressure Pain Detection Threshold (PPT) at the Brachioradialis Muscle Site	-69.33 kPa Standard Deviation 119.04	-37.31 kPa Standard Deviation 95.64	-25.75 kPa Standard Deviation 150.32	-27.77 kPa Standard Deviation 107.82

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: This analysis excludes individuals who either did not provide blood samples or whose values fell below the detection limit and thus did not pass quality control.

Change in serum levels of short-chain fatty acid (SCFA) butyric acid in response to the interventions. SCFA levels in serum will be measured using mass spectrometry.

Outcome measures

Measure	Diet Only Arm n=22 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=25 Participants 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.	Diet + Exercise Intervention Arm n=21 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=22 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Short Chain Fatty Acid Butyric Acid	345.61 ng/ml Standard Error 434.30	-233.17 ng/ml Standard Error 991.08	769.14 ng/ml Standard Error 3413.58	-36.67 ng/ml Standard Error 1082.93

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: This analysis excludes individuals who either did not provide blood samples or whose values fell belowthe detection limit and thus did not pass quality control.

Change in serum levels of short-chain fatty acid (SCFA) acetic acid in response to theinterventions. SCFA levels in serum will be measured using mass spectrometry.

Outcome measures

Measure	Diet Only Arm n=22 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=25 Participants 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.	Diet + Exercise Intervention Arm n=21 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=22 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Short Chain Fatty Acid Acetic Acid	306.32 ng/ml Standard Error 1406.99	-1081.01 ng/ml Standard Error 3561.43	110.37 ng/ml Standard Error 3334.09	-869.59 ng/ml Standard Error 3744.05

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: This analysis excludes individuals who did not provide blood samples or whose values failed quality control or for which results were not obtained

Change in Interleukin-6 (IL-6) inflammatory protein levels measured with the Olink for a subset of individuals. For Olink cytokine assay panels data is reported in either Normalized Protein eXpression units (NPX) units or absolute concentration units (pg/mL), with the lower limit of detection typically below 1 pg/mL for most assays.

Outcome measures

Measure	Diet Only Arm n=9 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=34 Participants 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.	Diet + Exercise Intervention Arm n=23 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=3 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Inflammatory Protein Interleukin-6 (IL-6) Levels	-0.70 pg/mL Standard Deviation 2.12	-0.25 pg/mL Standard Deviation 0.78	-0.12 pg/mL Standard Deviation 1.92	-1.85 pg/mL Standard Deviation 2.45

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: This analysis excludes individuals who did not provide blood samples or whose values failed quality control or for which results were not obtained

Change in Tumor Necrosis Factor (TNF) inflammatory protein levels measured with the Olink for a subset of individuals. For Olink cytokine assay panels data is reported in either Normalized Protein eXpression units (NPX) units or absolute concentration units (pg/mL), with the lower limit of detection typically below 1 pg/mL for most assays.

Outcome measures

Measure	Diet Only Arm n=9 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=34 Participants 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.	Diet + Exercise Intervention Arm n=23 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=3 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Tumor Necrosis Factor (TNF) Inflammatory Protein Levels	-0.72 pg/mL Standard Deviation 1.92	-0.39 pg/mL Standard Deviation 0.80	-0.34 pg/mL Standard Deviation 1.78	-0.52 pg/mL Standard Deviation 1.43

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: This analysis excludes individuals who did not provide blood samples or whose values failed quality control or for which results were not obtained

Change in Interferon gamma (IFN-γ) inflammatory protein levels measured with the Olink for a subset of individuals. For Olink cytokine assay panels data is reported in either Normalized Protein eXpression units (NPX) units or absolute concentration units (pg/mL), with the lower limit of detection typically below 1 pg/mL for most assays.

Outcome measures

Measure	Diet Only Arm n=9 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=34 Participants 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.	Diet + Exercise Intervention Arm n=23 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=3 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Inflammatory Protein Interferon Gamma (IFN-γ) Levels	0.04 pg/mL Standard Deviation 2.56	-0.72 pg/mL Standard Deviation 1.25	-0.36 pg/mL Standard Deviation 2.56	0.32 pg/mL Standard Deviation 1.72

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: This analysis excludes individuals who did not provide stool samples or whose values failed quality control or for which results were not obtained

The gut microbiome will be measured with shotgun metagenomic sequencing of stool samples and the Shannon Diversity Index will be calculated. The Shannon Diversity Index assesses both the richness (number of different species) and evenness (distribution of individuals among species) within the gut microbiome. A higher Shannon index indicates a more diverse microbiome, while a lower index suggests less diversity.

Outcome measures

Measure	Diet Only Arm n=22 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=34 Participants 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.	Diet + Exercise Intervention Arm n=22 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=2 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Changes in Gut Microbiome (Shannon Diversity Index)	-0.07 index Standard Deviation 0.26	-0.09 index Standard Deviation 0.31	-0.08 index Standard Deviation 0.33	0.01 index Standard Deviation 0.26

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: This analysis excludes individuals who did not provide blood samples or whose values failed quality control or for which results were not obtained

Serum levels of Endocannabinoid Anandamide (AEA) 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 Endocannabinoid Anandamide (AEA) in response to the intervention.

Outcome measures

Measure	Diet Only Arm n=23 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=25 Participants 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.	Diet + Exercise Intervention Arm n=20 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=22 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Serum Endocannabinoid Anandamide (AEA) Levels	0.05 nM Standard Deviation 0.66	0.05 nM Standard Deviation 0.70	0.31 nM Standard Deviation 0.77	0.32 nM Standard Deviation 0.82

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: This analysis excludes individuals who did not provide blood samples or whose values failed quality control or for which results were not obtained.

Serum levels of 2-arachidonoylglycerol (2-AG) Endocannabinoid 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 2-arachidonoylglycerol (2-AG) Endocannabinoid in response to the intervention.

Outcome measures

Measure	Diet Only Arm n=23 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm n=25 Participants 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.	Diet + Exercise Intervention Arm n=20 Participants The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=22 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Change in Serum 2-arachidonoylglycerol (2-AG) Endocannabinoid Levels	6.28 nM Standard Deviation 44.17	37.58 nM Standard Deviation 78.17	16.83 nM Standard Deviation 79.10	35.45 nM Standard Deviation 72.07

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: This analysis was conducted on a subset of samples from the Exercise-only and Diet + Exercise intervention arms, as it was designed to assess the effects of exercise alone, as well as the combined effects of exercise and diet, on gene expression. We specifically examined changes in the expression levels (fold change) of a predefined pain-related gene, calcium voltage-gated channel subunit alpha1 B, between baseline and follow-up.

Transcriptomics will be measured using RNA sequencing of blood samples collected at baseline and at follow-up (at the end of six weeks). RNA was extracted from whole blood, and sequencing libraries were prepared and analysed using standard RNA-seq pipelines.

Outcome measures

Measure	Diet Only Arm n=9 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm 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.	Diet + Exercise Intervention Arm The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=10 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Changes in Calcium Voltage-gated Channel Subunit alpha1 B Gene Expression Levels Using Transcriptomics on a Subset of Individuals	49.50 fold change Standard Error 140.48	—	—	26.37 fold change Standard Error 79.60

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: This analysis was conducted on a subset of samples from the Exercise-only and Diet + Exercise intervention arms, as it was designed to assess the effects of exercise alone, as well as the combined effects of exercise and diet, on gene expression. We specifically examined changes in the expression levels (fold change) of a predefined pain-related gene, solute carrier family 12 member 5, between baseline and follow-up.

Transcriptomics will be measured using RNA sequencing of blood samples collected at baseline and at follow-up (at the end of six weeks). RNA was extracted from whole blood, and sequencing libraries were prepared and analysed using standard RNA-seq pipelines.

Outcome measures

Measure	Diet Only Arm n=9 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm 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.	Diet + Exercise Intervention Arm The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=10 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Changes in Solute Carrier Family 12 Member 5 Gene Expression Levels Using Transcriptomics on a Subset of Individuals	20.75 fold change Standard Error 59.51	—	—	14.02 fold change Standard Error 41.60

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: This analysis was conducted on a subset of samples from the Exercise-only and Diet + Exercise intervention arms, as it was designed to assess the effects of exercise alone, as well as the combined effects of exercise and diet, on gene expression. We specifically examined changes in the expression levels (fold change) of a predefined pain-related gene, sodium voltage-gated channel alpha subunit 11, between baseline and follow-up

Transcriptomics will be measured using RNA sequencing of blood samples collected atbaseline and at follow-up (at the end of six weeks). RNA was extracted from whole blood,and sequencing libraries were prepared and analysed using standard RNA-seq pipelines.

Outcome measures

Measure	Diet Only Arm n=9 Participants The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks.	Exercise Only Arm 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.	Diet + Exercise Intervention Arm The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time.	Placebo Arm n=10 Participants The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks.
Changes in Sodium Voltage-gated Channel Alpha Subunit 11 Gene Expression Levels Using Transcriptomics on a Subset of Individuals	31.97 fold change Standard Error 90.21	—	—	12.26 fold change Standard Error 33.70

Adverse Events

Placebo Arm

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Diet Only Arm

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Exercise Only Arm

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Diet + Exercise Intervention Arm

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo Arm n=27 participants at risk The participants in the placebo/control arm will be required to take 10g of maltodextrin for the same period of 6 weeks. Maltodextrin (Placebo): 10g/ day which can be consumed by adding to breakfast cereal/ smoothie/ yogurt or drink of choice	Diet Only Arm n=26 participants at risk The participants in the dietary intervention arm will be required to take 20g of inulin for a period of 6 weeks. Inulin Fibre supplement: 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.	Exercise Only Arm n=40 participants at risk 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. Exercise: 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.	Diet + Exercise Intervention Arm n=24 participants at risk The participants in this arm will be required to take 20g of inulin for a period of 6 weeks and doing exercise at the same time. Inulin Fibre supplement: 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. Exercise: 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.
Gastrointestinal disorders Wind and bloating	0.00% 0/27 • Day 1 through Day 42 (daily assessments, 7 days/week)	38.5% 10/26 • Number of events 10 • Day 1 through Day 42 (daily assessments, 7 days/week)	0.00% 0/40 • Day 1 through Day 42 (daily assessments, 7 days/week)	54.2% 13/24 • Number of events 13 • Day 1 through Day 42 (daily assessments, 7 days/week)

Additional Information

Dr Afroditi Kouraki

University of Nottingham

Phone: 0115 8231676

Email: afroditi.kouraki1@nottingham.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place