The Effect of Diet and Exercise on ImmuNotherapy and the Microbiome (EDEN)

Background:

The human gut microbiome is a topic of growing research interest because it modulates

many systems, including immune function; and, alterations of the microbiome have been

associated with the development of many diseases, including cancer.

Optimization of the gut microbiome can increase the probability of responding to immune

checkpoint inhibitor therapy with responders exhibiting a higher level of gut microbial

diversity than non-responders. Therefore, efforts are underway to investigate the effects

of

modulating the microbiome on response to immune checkpoint inhibitor therapy.

Diet is a major modulator of the gut microbiome. In particular, a high-fiber, plant-based

diet promotes greater gut microbial diversity while diets high in animal fats and protein

are associated with lower gut microbial diversity.

Exercise has been shown to increase gut microbial diversity independent of diet in both

mice and humans. In addition, exercise has long been known to lower cancer risk and

improve outcomes in cancer patients, possibly through its ability to enhance immune

function.

Although diet and exercise prescriptions are cost-effective and implementable on a large

scale, poor compliance is a major issue. Acceptance and Commitment Training (ACT) can

help improve participant engagement and compliance with lifestyle change recommendations.

In melanoma participants, we hypothesize that the combination of a high-fiber,

plant-based diet and exercise will increase gut microbial diversity and potentially

increase the probability of responding to immune checkpoint inhibitor therapy.

Objectives:

To determine the feasibility of conducting a decentralized clinical trial involving diet

and exercise prescriptions with stool sample collections in melanoma participants who

will be undergoing treatment with immunotherapy.

Eligibility:

- Adults with melanoma who will be undergoing treatment with one of the following

immunotherapy options: ipilimumab and nivolumab, relatlimab and nivolumab,

pembrolizumab, or nivolumab.

- Adequate organ function as defined by the liver, kidney, and hematologic laboratory

testing.

- Participants who have recently used antibiotics, probiotics, fiber supplements, or

any other products/medications that can significantly alter the gut microbiome will

be excluded.

Design:

Feasibility trial wherein participants will be randomized in a 1-to-1 fashion to the

following arms:

Intervention Arm: 30 participants will be instructed to adopt a high-fiber, plant-based

diet and to engage in at least 150 minutes of moderate or 75 minutes of vigorous

intensity exercise per week.

Control Arm: 30 participants will be educated on general healthy eating and exercise

guidelines, but they will not be instructed to change their behavior.

All participants will be asked to periodically record dietary intake (in the MyFitnessPal

app or other logs, if needed), to wear a Garmin (trademark) physical activity tracker,

and to collect stool samples periodically. Feasibility will be determined by assessing

whether greater than or equal to 60 percent of participants in each arm adhere to their

respective protocols.