Crohn's Disease (CD), Rheumatoid Arthritis (RA), Ulcerative Colitis (UC)
Conditions
Keywords
ketogenic diet, carnivore diet, rheumatoid arthritis, inflammatory bowel disease, ulcerative colitis, crohn's disease, autoimmunity, randomized controlled trial, dietary intervention, lion diet, nutritional therapy
Brief summary
This study is a randomized controlled clinical trial evaluating whether two therapeutic dietary approaches - a ketogenic diet and a carnivore (lion) diet - can improve quality of life, reduce symptoms, and influence measures of disease activity in adults with inflammatory bowel disease \[ulcerative colitis and Crohn's disease\] (IBD) or rheumatoid arthritis (RA). Participants will be randomized into one of three groups: 1) Ketogenic Diet, 2) Carnivore (Lion) Diet or 3) Wait-List Control. Participants randomized to a dietary group (ketogenic diet or carnivore diet) will be provided guidance on their specific dietary therapy and answer questions about their symptoms and quality of life at different intervals over a 24 week period. Participants will also complete laboratory testing at different intervals to assess for changes in nutritional status, cardiometabolic health and markers of immune activation and inflammation. Participants initially placed on the wait-list group will be asked similar questions about their symptoms and quality of life and complete the same laboratory testing as participants in a dietary group. Participants on the wait list will then be compared to participants following a specific dietary pattern to assess for any differences between the 2 groups. After 12 weeks, participants on the wait list will be randomized to a dietary group (ketogenic diet or carnivore diet) and followed in a similar fashion for an additional 12 week period.
Detailed description
The primary goal of this study is to determine whether ketogenic or carnivore dietary therapy improves, health-related quality of life, disease specific symptom burden or objective inflammatory markers in patients with a history of IBD or RA. Given the limited prospective data on carnivore (lion) diet approaches for addressing autoimmune conditions, the study aims to assess feasibility of implementation as well as overall safety including the documentation of common adverse events, changes to nutritional status or changes to cardiometabolic status including blood lipids. Total participation time is approximately 27 weeks including a 3-week baseline run-in and a 24-week dietary intervention period divided into 2, 12-week phases. Randomization and 3 week run-in period Participants will be randomized in a 2-2-2 schema, stratified by disease state (IBD or RA), to the carnivore (lion) diet, ketogenic diet, or placed on a wait-list. Participants will receive an at-home blood ketone and blood glucose monitoring device and a digital body composition scale. Participants will discontinue any supplements started within one month of study enrollment. Participants will then complete questionnaires and laboratory testing across several areas to include: Baseline quality-of-life, psychometric, and disease-specific symptom questionnaires Baseline body composition assessment and a historical food frequency questionnaire Baseline qualitative and quantitative analysis of self reported dietary intake Baseline at-home finger-stick blood ketone and blood glucose monitoring Baseline fasted blood collection and at-home stool collection Initial dietary intervention and support Participants randomized into a dietary intervention group will receive educational materials, including recommended foods and structured meal plans, with ongoing virtual access to medical and nutrition providers. Participants will join scheduled group telehealth sessions tailored to their dietary intervention to review study procedures, ask questions, and receive support within a community of fellow participants. Participants will receive ongoing telehealth monitoring from the medical and nutritional staff. Participants will complete certain study questionnaires around dietary adherence, progress and satisfaction at different intervals throughout the study. Participants will also also complete qualitative and quantitative dietary journals alongside at home blood ketone and blood glucose at various intervals throughout the study. Midpoint questionnaires and testing After the first 12 weeks of their specified dietary intervention, participants will complete questionnaires and testing similar to their baseline to assess for any initial changes. Participants initially placed on the wait-list will be asked similar questions about their symptoms and quality of life and complete the same laboratory testing as participants in a dietary group for the purposes of comparison at 12 weeks. Following the completion of their midpoint testing, participants on the wait list will be randomized to a dietary group (ketogenic diet or carnivore diet) and complete the same initial 12 week dietary program as those originally randomized to a dietary group. Individuals in the original dietary groups will continue for an additional 12 weeks in their specified dietary interventions OR voluntarily elect to "cross-over" into the other dietary intervention arm with the approval of the clinical team. Participants in either dietary intervention group will continue to receive ongoing support, education and virtual access to the medical and nutritional team. Final Questionnaires and Testing After 24 weeks (2, 12 week dietary phases), all study participants will repeat baseline study questionnaires and laboratory testing for the sake of comparison of key outcome measures at 24 weeks.
Interventions
BEHAVIORALKetogenic diet
The ketogenic diet is a high fat, moderate protein, and very low carbohydrate nutritional approach designed to shift the body's primary energy source from glucose to ketones, compounds produced in the liver from fat metabolism. This state of nutritional ketosis typically occurs when carbohydrate intake is restricted to 20-50 grams per day, though the exact threshold varies based on individual factors such as muscle mass, insulin sensitivity, and physical activity. Participants will receive nutritional guidance for the ketogenic diet in a virtual setting via both synchronous and asynchronous engagement including group telehealth sessions, dietary education guides/food lists, quantitative sample meals plans and ongoing messaging capacity with the clinical team for the duration of the dietary intervention.
BEHAVIORALCarnivore (Lion) Diet
The carnivore (lion) diet is a more restrictive form of a ketogenic diet that is intended as an elimination dietary protocol composed exclusively of ruminant meats (beef, lamb, bison, venison, goat, moose, elk), salt, and water. A broader carnivore diet includes more animal foods such as additional meats, fish, eggs, and some dairy. It excludes, however, all plant foods including vegetables, fruits, grains, legumes, nuts, seeds, or plant-derived oils. Participants will receive nutritional guidance for the carnivore (lion) and the broader carnivore diet in a virtual setting via both synchronous and asynchronous engagement including group telehealth sessions, dietary education guides/food lists, quantitative sample meals plans and ongoing messaging capacity with the clinical team for the duration of the dietary intervention.
Sponsors
Fuller Research Foundation
Resilient Roots: Functional Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
There are 2 planned randomizations. The first randomization will create 3 arms (ketogenic diet, carnivore \[lion\] diet and a wait-list control). The second randomization occurring after 12 weeks will apply ONLY to participants in the wait-list control group and will create 2 additional, but interventionally similar arms (wait-list -\> ketogenic diet and wait-list -\> carnivore \[lion\] diet). The final 2, additional arms are hypothetical, but distinct study arms that will be created at 12 weeks and voluntarily (no randomization) from participants of either the original ketogenic diet or carnivore \[lion\] diet intervention arms. Participants at 12 weeks can voluntarily elect to cross-over to the other dietary arm for the final 12 weeks of the study intervention (ketogenic diet -\> carnivore \[lion\] diet) or carnivore \[lion\] diet -\> ketogenic diet).
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with medically verifiable IBD or medically verifiable RA * Current personal residence in the continental U.S. * Willingness and ability to follow dietary protocols
Exclusion criteria
* Inability to provide consent * Individuals with Type 1 or Type II Diabetes on prescription medications including insulin * Outside of the age or BMI criteria * No medically definitive or verifiable diagnosis of IBD or RA * History of strictures or fistula (IBD) * History of blood transfusion in the previous 6 months * Pregnancy * 6 months Postpartum * Breastfeeding * On other medications outside of FDA approved medications * Current initiation of disease modifying or biologic medication within the past 2 months * Unable to complete, for any reason, the initial 3-week run-in period prior to the beginning of the formal study intervention * Non-English Speaking * Organ failure of any kind including heart, liver and kidney failure or disease * History of malignancy within the last year prior to enrollment * Red meat allergy, alpha-gal allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in health-related quality of life measured using the 36-Item Short Form Health Survey (SF-36) | From baseline to 24 weeks | The SF-36 consists of 8 subscales including: physical functioning, role limitations due to physical health (physical role functioning), role limitations due to emotional problems (emotional role functioning), vitality, mental health, social role functioning, bodily pain and general health. Scores for each subscale will be on a 0-100 scale with higher scores generally reflecting better health or less functional impairment for that respective subscale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Rheumatoid Arthritis Disease Activity Index-5 Questionnaire (RADAI-5) | From baseline to 12 and 24 weeks | RADAI-5 is a 5-item questionnaire designed to assess rheumatoid arthritis symptomatic activity. Scores for each item are on a 0-10 scale. Higher scores indicate worse outcome/symptoms. \*\*RA only\*\* |
| Change in Routine Assessment of Patient Index Data (RAPID-3) | From baseline to 12 and 24 weeks | RAPID-3 is a questionnaire used to monitor rheumatoid arthritis symptoms and disease activity by measuring a participant's functional status, pain, and overall perception of health. Scores range from 0-30; higher scores indicate worse outcome." \*\*RA only\*\* |
| Change in Inflammatory Bowel Disease Symptom Inventory - Short Form (IBDSI-SF) | From baseline to 12 and 24 weeks | The IBDSI-SF measures the frequency and severity of IBD related symptoms as well as their interference with overall functioning and daily activities. We are using a version with 23 questions that excludes the bowel complications subscale - questions 24 and 25 related to fistulas given this as an exclusion criteria. 22 of the 23 questions are scored on a 0-4 scale with higher scores reflecting worse outcome/symptoms. 1 question is rated on a 0-2 scale with a higher score reflecting a worse outcome/symptom. Total scores range from 0-90, higher scores indicating worse outcomes. \*\*IBD only\*\* |
| Change in fecal calprotectin | From baseline to 12 and 24 weeks | Fecal calprotectin is a well established biomarker for intestinal inflammation and validated for diagnosis and monitoring of disease activity in patients with IBD. \*\*IBD only\*\* |
| Change in immune and inflammatory serology | From baseline to 12 and 24 weeks | Participants will have associated immune and inflammatory serology to include: 1. Total white blood cell count (WBC), 2. Immune cell differential \[neutrophils, lymphocytes, monocytes, eosinophils, and basophils\] 3. High sensitivity C-reactive protein (hs-CRP), 4. Erythrocyte sedimentation rate (ESR). Each marker can be assessed independently, but the markers collectively are typically associated together in systemic autoimmune disease and are, hence, described collectively here. |
| Change in point of care (at-home) blood ketones (beta-hydroxybutyrate) | From baseline to the end of the study intervention at 24 weeks | Participants will collect periodic at-home measurements of blood ketones (beta-hydroxybutyrate) via a provided blood ketone meter. At-home blood ketones will be primarily utilized to assess adherence to prescribed dietary interventions or self implementation of a interventional dietary strategy for participants on the wait-list. |
| Change in point of care (at-home) blood glucose | From baseline to the end of the study intervention at 24 weeks | Participants will collect periodic at-home measurements of blood glucose via a provided blood glucose meter. At-home blood glucose measurements will be primarily utilized to assess adherence and safety of the prescribed dietary regimens or self implementation of a interventional dietary strategy for participants on the wait-list. |
Countries
United States
Contacts
CONTACTRobert D Abbott, MD
CONTACTEmily Palmer, MS, CNS
PRINCIPAL_INVESTIGATORRobert D Abbott, MD
Resilient Roots: Functional Medicine
Outcome results
None listed