MelanomaNCT04866810
The Effect of Diet and Exercise on ImmuNotherapy and the Microbiome (EDEN)
A study testing Intervention Arm in people with Melanoma, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
Background: The gut microbiome is made up microorganisms. These include the good and bad bacteria that live in the digestive tract. Changes in the gut microbiome have been linked to the development of cancer. Researchers want to learn more about the effects of modulating the microbiome with diet and exercise. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Melanoma
- What is being tested?
- Intervention Arm
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesUnited States
- Study dates
- 25 Jul 2023to 31 Oct 2028
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have histologically or cytologically confirmed melanoma that has not been treated with any systemic therapy in the past 30 days.
- Participants must be planning to undergo immunotherapy treatment with one of the following options: ipilimumab and nivolumab, relatlimab and nivolumab, pembrolizumab, or nivolumab. Note: This treatment is permissible to have started up to 14 days prior to completion of baseline assessments on this study to still be eligible for enrollment.
- Age >= 18 years and English speaking. English-language ability is required because a portion of the study involves reading and responding to English-language questionnaires, along with creating a free response spoken answer to a question, where the information will be transcribed and analyzed.
- Willingness and capability to comply with diet and exercise prescriptions, use the MyFitnessPal app, wear the Garmin (trademark) device, complete surveys, and provide stool samples. Participants must own a smartphone capable of running the MyFitnessPal and Garmin Connect (trademark) apps.
- ECOG performance status <=2 (Karnofsky >60 percent).
- The ability of the subject to understand and the willingness to sign a written informed consent document.
Who cannot join
- Participants who are receiving any investigational agents.
- Any concurrent malignancy that requires active systemic therapy
- Any health condition that requires treatment with cytotoxic chemotherapy or targeted therapy
- Medical contraindications to the study diet and/or exercise prescriptions as determined by a physician
- Self-reported dietary and/or exercise restrictions that would preclude adherence to the study diet and exercise prescriptions
- Systemic antibiotic use within the past 30 days
Show all 14Show fewer
- Use of probiotic supplements (probiotic foods such as yogurt, kefir, sauerkraut, etc., are permissible), fiber supplements, bile acid
- sequestrants, weight loss supplements, or appetite suppressants within the last 30 days.
- Women known to be pregnant or lactating are excluded from the study because it is unknown if the study diet and exercise prescriptions may have deleterious effects on the child and/or mother in the context of pregnancy/breastfeeding.
- Current smoker or < 8 weeks since smoking cessation. There is evidence that smoking may alter the microbiome.
- Heavy drinker defined as >14 alcoholic drinks per week
- Current illicit drug use. There is evidence that illicit drug use may alter the microbiome.
- Diagnosis of diabetes mellitus type I or II that requires treatment
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Loma Linda University
Loma Linda, California, 92350
About this study
Background:
The gut microbiome is made up microorganisms. These include the good and bad bacteria that live in the digestive tract. Changes in the gut microbiome have been linked to the development of cancer. Researchers want to learn more about the effects of modulating the microbiome with diet and exercise.
Read more
Objective:
To see if nutritional intake and physical activity change the gut microbiome in people with melanoma.
Eligibility:
Adults age 18 and older with previously untreated melanoma who will be getting immunotherapy treatment for their disease.
Design:
Participants will not have visits at NIH. They will have phone calls or videocalls.
Participants will be screened with a medical history and medical record review.
Participants will give stool samples. They will fill out surveys about their health, feelings, diet, and exercise.
Participants will be put in 1 of 2 groups. They will follow their group s plan for 4 months. They will be contacted throughout the study.
Intervention Group participants will follow a plant-based, high-fiber diet. They will do at least 150 minutes of moderate or 75 minutes of high-intensity exercise per week. They will have sessions with psychology staff to help them make positive lifestyle changes.
Control Group participants will be taught healthy eating and exercise guidelines. But they will not be asked to change their diet or exercise habits.
All participants will record what they eat in the MyFitnessPal app. They will get a scale to measure their weight each week. They will wear a Garmin(R) physical activity tracker at all times. They can take the tracker off to bathe or shower.
Participation will last for 6 months....
Read the detailed description
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.
- Conditions
- Melanoma
- Being tested
- Intervention Arm, Control
- Keywords
- Ipilimumab, Pembrolizumab, relatlimab, nivolumab, Lymphocyte activation gene 3, LAG-3, Garmin, anti PD-1/PD-L1, Acceptance and Commitment Training (ACT)
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intervention ArmBehavioural
High fiber, plant based diet + exercise prescription with ACT sessions
ControlBehavioural
Standard diet and exercise recommendations
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Intervention Receives: Behavioral: Intervention Arm |
| 2 | Other | Control- Standard diet and Exercise Receives: Behavioral: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
feasibility of conducting a decentralized clinical trial involving diet and exercise prescriptions with stool sample collections in patients receiving immunotherapy
Assessing compliance with study requirements (e.g., logging diet, physical activity per the fitness tracker, completing PROs), assessed per arm; 60% compliance is a success
Measured: 43 days
Secondary outcomes (3)
Progression Free Survival (PFS)
PFS will be evaluated on the two arms using a Kaplan-Meir curve and compared using a log-rank test.
Measured: through day 113
Quality of Life (QOL)
QOL factors in the PRO surveys will be measured using T-scores and T-tests or ANOVA.
Measured: baseline, day 43 and day 113
Objective Response Rate (ORR)
Response rates will be compared using a one-tailed Fisher's exact test to determine if the response rate exhibits a trend toward improvement with lifestyle intervention
Measured: through day 113
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2021
- Study start25 Jul 2023
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Oct 2028 (estimated)
Why it stopped: On hold pending planned interim analysis.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- James L Gulley, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04866810
- Sponsor's protocol ID
- 10000251
- Other IDs
- 000251-C
- Status last verified
- 15 Oct 2026
- First submitted
- 29 Apr 2021
- Last updated
- 19 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Diet and Exercise on ImmuNotherapy and the Microbiome (EDEN)
- ClinicalTrials.gov ID
- NCT04866810
- Acronym / sponsor ID
- 10000251
- Conditions
- Melanoma
- Keywords
- Ipilimumab, Pembrolizumab, relatlimab, nivolumab, Lymphocyte activation gene 3, LAG-3, Garmin, anti PD-1/PD-L1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: On hold pending planned interim analysis.
- Enrolment
- 35 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 25 Jul 2023 (actual)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 Oct 2028 (estimated)
- First posted
- 30 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
The gut microbiome is made up microorganisms. These include the good and bad bacteria that live in the digestive tract. Changes in the gut microbiome have been linked to the development of cancer. Researchers want to learn more about the effects of modulating the microbiome with diet and exercise.
Objective:
To see if nutritional intake and physical activity change the gut microbiome in people with melanoma.
Eligibility:
Adults age 18 and older with previously untreated melanoma who will be getting immunotherapy treatment for their disease.
Design:
Participants will not have visits at NIH. They will have phone calls or videocalls.
Participants will be screened with a medical history and medical record review.
Participants will give stool samples. They will fill out surveys about their health, feelings, diet, and exercise.
Participants will be put in 1 of 2 groups. They will follow their group s plan for 4 months. They will be contacted throughout the study.
Intervention Group participants will follow a plant-based, high-fiber diet. They will do at least 150 minutes of moderate or 75 minutes of high-intensity exercise per week. They will have sessions with psychology staff to help them make positive lifestyle changes.
Control Group participants will be taught healthy eating and exercise guidelines. But they will not be asked to change their diet or exercise habits.
All participants will record what they eat in the MyFitnessPal app. They will get a scale to measure their weight each week. They will wear a Garmin(R) physical activity tracker at all times. They can take the tracker off to bathe or shower.
Participation will last for 6 months....
Detailed description
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Behavioral: Intervention ArmIntervention |
| 2 | Other | Behavioral: ControlControl- Standard diet and Exercise |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Participants must have histologically or cytologically confirmed melanoma that has not been treated with any systemic therapy in the past 30 days.
- Participants must be planning to undergo immunotherapy treatment with one of the following options: ipilimumab and nivolumab, relatlimab and nivolumab, pembrolizumab, or nivolumab. Note: This treatment is permissible to have started up to 14 days prior to completion of baseline assessments on this study to still be eligible for enrollment.
- Age >= 18 years and English speaking. English-language ability is required because a portion of the study involves reading and responding to English-language questionnaires, along with creating a free response spoken answer to a question, where the information will be transcribed and analyzed.
- Willingness and capability to comply with diet and exercise prescriptions, use the MyFitnessPal app, wear the Garmin (trademark) device, complete surveys, and provide stool samples. Participants must own a smartphone capable of running the MyFitnessPal and Garmin Connect (trademark) apps.
- ECOG performance status <=2 (Karnofsky >60 percent).
Key exclusion criteria (14 listed)
- Participants who are receiving any investigational agents.
- Any concurrent malignancy that requires active systemic therapy
- Any health condition that requires treatment with cytotoxic chemotherapy or targeted therapy
- Medical contraindications to the study diet and/or exercise prescriptions as determined by a physician
- Self-reported dietary and/or exercise restrictions that would preclude adherence to the study diet and exercise prescriptions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intervention ArmHigh fiber, plant based diet + exercise prescription with ACT sessions | Behavioural | 1 |
| ControlStandard diet and exercise recommendations | Behavioural | 2 |
Primary outcome
feasibility of conducting a decentralized clinical trial involving diet and exercise prescriptions with stool sample collections in patients receiving immunotherapy
Time frame: 43 days
Assessing compliance with study requirements (e.g., logging diet, physical activity per the fitness tracker, completing PROs), assessed per arm; 60% compliance is a success
3 secondary outcomes
Progression Free Survival (PFS)
Time frame: through day 113
Quality of Life (QOL)
Time frame: baseline, day 43 and day 113
Objective Response Rate (ORR)
Time frame: through day 113
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James L Gulley, M.D. principal investigator
National Cancer Institute (NCI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intervention Arm in people with Melanoma, run by National Cancer Institute (NCI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
feasibility of conducting a decentralized clinical trial involving diet and exercise prescriptions with stool sample collections in patients receiving immunotherapy (time frame: 43 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.