Trials / Not Yet Recruiting

Not Yet RecruitingNCT07417891

Ketogenic Diet to Reduce Osteoarthritis Pain in MCI

Status: Not Yet Recruiting
Phase: N/A
Study type: Interventional
Enrollment: 10 (estimated)

Sponsor: University of Kansas Medical Center · Academic / Other
Sex: All
Age: 55 Years – 75 Years
Healthy volunteers: Not accepted

Summary

Osteoarthritis and mild cognitive impairment are common conditions that share underlying biological processes related to metabolism and inflammation. This study will examine whether a well-formulated ketogenic diet influences pain, physical function, and cognitive outcomes in adults with osteoarthritis and mild cognitive impairment. Participants will follow a supervised ketogenic dietary intervention, with assessments conducted before and after the intervention to evaluate changes in symptoms and related biological markers. The goal of this study is to better understand shared mechanisms between joint pain and cognitive health and to explore whether a ketogenic dietary approach may support symptom management in these populations.

Detailed description

OA and dementia are two leading contributors to disability worldwide. Although traditionally studied separately, accumulating evidence indicates substantial overlap in their underlying inflammatory, metabolic, and neuroimmune pathways. Chronic OA pain is associated with systemic inflammatory mediators, increased peripheral nociceptor sensitization, impaired descending inhibition, and central neuroinflammation driven by microglia and astrocyte activation. These same mechanisms contribute to cognitive decline, reduced synaptic plasticity, hippocampal vulnerability, and progression from MCI to ADRD. In aging adults, chronic pain accelerates cognitive decline and increases risk for dementia, and cognitive impairment exacerbates pain-related disability. Neuroinflammation-particularly microglial activation and NLRP3 inflammasome signaling-is a shared mechanistic link between the two conditions. Identifying interventions that target this shared biology is crucial for improving outcomes for older adults with comorbid pain and cognitive decline. The ketogenic diet has demonstrated therapeutic effects in multiple neurological, metabolic, and inflammatory conditions. Mechanisms include suppression of the NLRP3 inflammasome, improved mitochondrial efficiency, enhanced lipid metabolism via TREM2-associated pathways, reduced oxidative stress, reduced systemic inflammation, glycemic control, and modulation of gut microbiota. Preclinical data show that ketone bodies improve cognitive function and reduce neuroinflammation in models of AD. Human studies demonstrate the feasibility and potential cognitive benefit of WFKD in ADRD populations and post-concussion syndrome. Additionally, this study team recently investigated the impact of an 8-week WFKD on modifiable risk factors associated with metabolic syndrome, on gut microbiota structure, and RNASeq in healthy, middle-aged adults. However, the application of a WFKD to individuals with OA and early cognitive impairment is unexplored. Our team has conducted two previous clinical trials and is currently analyzing outcomes of an NIA-funded clinical trial using the WFKD. Participants from these trials have successfully adopted the WFKD, evidenced by objective and reported ketone body production and macronutrient profile of dietary intake. The WFKD used in these trials improved micronutrient intake and intake of non-starchy vegetables, and suggests that the WFKD may benefit cognition in patients with AD and symptoms in patients with post-concussion syndrome. This population is particularly relevant given the aging US population, the high prevalence of OA-associated chronic pain, the presence of early neuroinflammation and neurodegeneration, poor diet quality contributing to systemic inflammation, and heightened vulnerability to cognitive decline, reduced quality of life, and hospitalization/institutionalization. Understanding how a WFKD influences pain, neuroinflammation, central sensitization, cognitive performance, and biologic indicators from the gut and peripheral nerves will provide critical insight into mechanistic targets for future clinical trials.

Conditions

Interventions

Type	Name	Description
OTHER	Well-formulated ketogenic diet	This is a very low carbohydrate eating pattern that is higher in fat with adequate protein. This approach focuses on a nutrient dense, whole foods approach to a ketogenic diet and recommends 4-6 servings of non-starchy vegetables per day, 1/4 cup of berries per day, daily intake of nuts/seeds, fatty fish 2-3 times per week, and an emphasis on healthy fats like avocado, nuts, and olive oil.

Timeline

Start date: 2026-03-01
Primary completion: 2026-10-01
Completion: 2026-12-01
First posted: 2026-02-18
Last updated: 2026-02-18

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT07417891. Inclusion in this directory is not an endorsement.