Knee Osteoarthritis
Conditions
Keywords
Inulin, Prebiotic, Lipopolysaccharide, Inflammation, Knee pain, Older adults
Brief summary
This study will test whether inulin, a type of dietary fiber, can reduce inflammation in older adults with knee osteoarthritis. Inflammation in the body may contribute to both joint pain and the progression of osteoarthritis. Inulin is a prebiotic fiber that may improve gut health and reduce lipopolysaccharide (LPS), a marker of bacterial products in the blood that is linked to inflammation. In this trial, participants with knee osteoarthritis will be randomly assigned to receive either inulin or a placebo (maltodextrin) for 8 weeks. The study will measure changes in blood LPS levels, knee pain, and other markers of inflammation. The goal is to determine whether inulin supplementation can improve pain and reduce inflammation in people with knee osteoarthritis.
Detailed description
Knee osteoarthritis (OA) is a leading cause of pain and disability among older adults. Low-grade systemic inflammation has been implicated in OA pathogenesis, and bacterial products such as lipopolysaccharide (LPS) translocated from the gut microbiome may contribute to joint inflammation. Inulin-type fructans are non-digestible carbohydrates classified as prebiotic fibers. By modulating the gut microbiome, inulin has been shown to promote the growth of beneficial bacteria and to increase short-chain fatty acid (SCFA) production, which may help reduce systemic LPS levels and inflammation. This is a single-center, randomized, double-blind, placebo-controlled clinical trial of participants aged 40 years or older with radiographically confirmed knee OA and significant knee pain. Participants will be randomized in a 1:1:1 ratio to receive 10 g/day inulin, 15 g/day inulin, or placebo (maltodextrin) for 8 weeks. The primary outcome is change in serum LPS from baseline to 8 weeks in the combined inulin groups compared to placebo. The study hypothesis is that inulin supplementation will reduce circulating LPS and improve knee pain outcomes, supporting the role of gut microbiome modulation in the management of OA-related inflammation.
Interventions
DRUGinulin
Inulin is a fermentable prebiotic fiber derived from chicory root. For this study, inulin is packaged into single-dose sachets containing 5 g, 10 g, or 15 g of powder. Participants in the 10 g arm escalate from 5 g/day for 3 days to 10 g/day, then continue with sachets containing a 2:1 blend of inulin and maltodextrin to provide a daily 10 g inulin dose. Participants in the 15 g arm escalate from 5 g/day for 3 days, 10 g/day for 4 days, then 15 g/day for the remaining 8 weeks. Sachets are mixed with food or beverage and taken once daily with the largest meal.
DRUGMaltodextrin (Placebo)
Maltodextrin is a carbohydrate powder widely used as a food additive. For this study, maltodextrin is used as the placebo comparator. It is packaged into single-dose sachets identical in appearance and taste to inulin sachets. Participants receive escalating doses (5 g/day for 3 days, 10 g/day for 4 days, then 15 g/day) for a total of 8 weeks. Sachets are mixed with food or beverage and taken once daily with the largest meal.
Sponsors
Yale University
VA Connecticut Healthcare System
National Center for Complementary and Integrative Health (NCCIH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Inulin and placebo are identical in appearance, taste, and packaging. Randomization is managed by the investigational pharmacy; study staff, investigators, and participants remain blinded.
Intervention model description
Participants are randomized in a 1:1:1 ratio to placebo, 10 g/day inulin, or 15 g/day inulin for 8 weeks.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated informed consent form. * Stated willingness to comply with all study procedures and availability for the duration of the study (8 weeks). * Male or female, aged ≥ 40 years. * Established patient in the VA Connecticut Healthcare System * At least one knee with pain severity in the past week ≥ 4/10 on numerical rating scale (NRS) * Self-reported knee pain on most days of the prior month. * Diagnosed with knee osteoarthritis (Kellgren-Lawrence grade 2-4 on radiographic imaging within the past 2 years). * Ability to take oral powder supplements and willingness to adhere to the inulin/placebo daily regimen. * Agreement to adhere to lifestyle considerations (see Section 5.3) throughout study duration, including maintenance of current diet, physical activity, and avoidance of new dietary supplements or complementary therapies. * English-speaking and able to provide informed consent. * For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to continue such method during study participation.
Exclusion criteria
* Current diagnosis of pre-diabetes (impaired glucose tolerance) or diabetes mellitus (Type 1 or Type 2). * Use of antibiotics within the past 6 months. * Current use of medications known to significantly impact the gut microbiome (e.g., proton pump inhibitors, disease-modifying antirheumatic drugs, GLP-1 receptor agonists). * Use of anti-inflammatory dietary supplements (e.g., turmeric, omega-3 fatty acids) within the past 30 days. * Participation in another interventional study or use of an investigational drug within the past 30 days. * Current use of complementary or integrative therapies for knee OA including tai chi, acupuncture or yoga. * Known allergy or intolerance to components of the study intervention, including inulin or maltodextrin. * The presence of significant gastrointestinal disease that may interfere with the intervention or outcomes, such as inflammatory bowel disease or active peptic ulcer disease. * Any medical, psychological, or behavioral condition that, in the opinion of the investigators, would place the participant at undue risk, interfere with study participation or adherence, or compromise data integrity. * Current diagnosis of alcohol use disorder * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in serum lipopolysaccharide (LPS) concentration from baseline to 8 weeks | Baseline and 8 weeks | Serum LPS levels will be measured at baseline and at 8 weeks to evaluate the effect of inulin supplementation compared to placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in serum LPS concentration between 10 g and 15 g inulin groups | Baseline and 8 weeks | Dose-response effect of inulin supplementation on serum LPS levels. |
| Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) | Baseline and 8 weeks | Self-reported knee pain and function will be measured using the WOMAC scale. Higher scores indicate worse pain, stiffness, and functional limitations. Total possible score of 0-96. |
Countries
United States
Contacts
CONTACTEvelyn Hsieh, MD, PhD
PRINCIPAL_INVESTIGATOREvelyn Hsieh, MD, PhD
Yale University
Outcome results
None listed