CLL-IMPACT: A Clinical Nutrition Trial Investigating Immune and Metabolic Changes in Early-Stage CLL

This is a prospective, exploratory, single-arm pilot study designed as a pre-post comparison in which each participant serves as their own control. The aim of the trial is to investigate whether a short-term (4-week) whole-food, plant-based (WFPB) diet influences disease activity, immune function, and metabolism in patients with early-stage, treatment-naïve chronic lymphocytic leukemia (CLL) who are currently managed with a watch-and-wait strategy. Up to 50 participants will be enrolled.

The primary objective is to assess whether a WFPB diet impacts disease activity, as reflected by changes in absolute lymphocyte counts and other hematologic parameters. Secondary objectives include examining the effects of the dietary intervention on immune cell subsets, their signaling pathways, and cell-cell interactions. In addition, the study will evaluate changes in microbiome composition and related metabolic processes, as well as explore systemic metabolic shifts through targeted and untargeted omics analyses. These include metabolomics, lipidomics, and other exploratory omics approaches, conducted on a subset of participants.

Additional health-related outcomes will also be assessed. These include anthropometric and metabolic markers such as body weight, body mass index (BMI), body composition (lean mass and fat mass), blood glucose, lipid profiles, and systemic inflammatory markers. Stool samples will be analyzed for microbiome composition and metabolites, while blood samples will be used for flow cytometry-based immune profiling, signaling analyses, and exploratory omics assays.

The dietary intervention is defined as a whole-food, plant-based diet that excludes highly processed foods, minimizes intake of moderately processed foods, eliminates all animal-derived foods, and reduces consumption of sugar-sweetened and alcoholic products. Participants will be encouraged to eat to satiety without restriction on quantity. A certified dietary instructor will provide individualized counseling, taking into account each participant's baseline dietary habits and lifestyle. Adherence will be monitored through a food diary kept during the week prior to study initiation and throughout the 4-week intervention.

Study visits will take place at baseline (prior to dietary change), after 14 days, and after 28 days. At each visit, blood and stool samples will be collected, clinical assessments will be performed, and at day 0 and 28 body composition will be measured. The trial is exploratory in nature, aiming to generate hypotheses and mechanistic insights into the potential of a short-term dietary intervention to modulate disease biology and systemic metabolism in CLL.

Inclusion criteria

• Confirmed CLL diagnosis
• No previous treatments (watch and wait)
• Willingness to comply to a whole-food plant-based diet for 4 weeks
• Willingness to participate in a total of 3 blood drawings

Exclusion criteria

• Emergency interventions
• Patients that already follow a WFPB or vegan diet
• Progression of CLL that implicates need for treatment
• Insulin-dependent diabetes
• Taking lipid-lowering medications (e.g. statins)
• Body mass index (BMI) <20 And if in the opinion of the investigator there are any concerns regarding the ability of the patient to complete the study safely.