Ketogenic Diet to Reduce Osteoarthritis Pain in MCI
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Well-formulated ketogenic diet.
- Who it may be relevant to
- Registry conditions: Osteoarthritis (OA) of the Hip, Osteoarthritis (OA) of the Knee, Osteoarthritis (OA) of the Shoulder, Osteoarthritis. Basic parameters: 55 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Interventions
- 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.
Primary outcome measures
- Pain intensity and pain interference using a Visual Analog Scale [Time frame: From enrollment to the end of treatment at 8 weeks]
- Health-related quality of life using a Questionnaire [Time frame: From enrollment to end of treatment at 8 weeks]
- Physical Function via Functional Activities Questionnaire [Time frame: From enrollment to end of treatment at 8 weeks.]
- Montreal Cognitive Assessment (MoCA) for brief global cognitive screening [Time frame: From enrollment to end of treatment at 8 weeks.]
Secondary outcome measures (2)
- Central sensitization [Time frame: From enrollment to end of treatment at 8 weeks.]
- Ketone levels [Time frame: From enrollment to end of treatment at 8 weeks.]
Eligibility criteria
Inclusion criteria
- English speaking
- Diagnosis of major joint osteoarthritis
- Diagnosis of mild cognitive impairment
Exclusion criteria
- Diabetes that requires insulin
- Cancer requiring chemo- or radiation therapy in the last 2 years
- Cardiac event within 1 year
- Recent history of renal stones
- Diagnosis of fibromyalgia
- Already following a ketogenic diet
- Following a dietary pattern that does not allow for a ketogenic approach
- Unable to control one's diet
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 1 center
- University of Kansas Medical Center — Fairway
Identifiers
NCT: NCT07417891 · KDROPMCI