The Effect of Diet and Exercise on ImmuNotherapy and the Microbiome (EDEN)
Primary Purpose
Melanoma
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Intervention Arm
Control
Sponsored by
About this trial
This is an interventional other trial for Melanoma focused on measuring Ipilimumab, Pembrolizumab, relatlimab, nivolumab, Lymphocyte activation gene 3, LAG-3, Garmin, anti PD-1/PD-L1, Acceptance and Commitment Training (ACT)
Eligibility Criteria
- INCLUSION CRITERIA:
- Participants must have histologically or cytologically confirmed unresectable melanoma that has not been treated with any systemic therapy.
- Participants must be planning to undergo treatment with the combination of relatlimab and nivolumab immunotherapy. 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.
- Participants must have measurable disease, per RECIST 1.1.
- Age greater than or equal to 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%,).
- BMI 18.5 -35 kg/m2
- The ability of the subject to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
- Participants who are receiving any other 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
- 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.
Sites / Locations
- National Institutes of Health Clinical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
1
2
Arm Description
Intervention
Control- Standard diet and Exercise
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Progression Free Survival (PFS)
PFS will be evaluated on the two arms using a Kaplan-Meir curve and compared using a log-rank test.
Quality of Life (QOL)
QOL factors in the PRO surveys will be measured using T-scores and T-tests or ANOVA.
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
Full Information
NCT ID
NCT04866810
First Posted
April 29, 2021
Last Updated
July 28, 2023
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT04866810
Brief Title
The Effect of Diet and Exercise on ImmuNotherapy and the Microbiome (EDEN)
Official Title
The Effect of Diet and Exercise on ImmuNotherapy and the Microbiome (EDEN)
Study Type
Interventional
2. Study Status
Record Verification Date
July 26, 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 25, 2023 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
October 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
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 previously untreated, unresectable melanoma participants who will be undergoing treatment with relatlimab and nivolumab.
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% of participants in each arm adhere to their respective protocols.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Ipilimumab, Pembrolizumab, relatlimab, nivolumab, Lymphocyte activation gene 3, LAG-3, Garmin, anti PD-1/PD-L1, Acceptance and Commitment Training (ACT)
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Intervention
Arm Title
2
Arm Type
Other
Arm Description
Control- Standard diet and Exercise
Intervention Type
Behavioral
Intervention Name(s)
Intervention Arm
Intervention Description
High fiber, plant based diet + exercise prescription with ACT sessions
Intervention Type
Behavioral
Intervention Name(s)
Control
Intervention Description
Standard diet and exercise recommendations
Primary Outcome Measure Information:
Title
feasibility of conducting a decentralized clinical trial involving diet and exercise prescriptions with stool sample collections in patients receiving immunotherapy
Description
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
Time Frame
43 days
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
PFS will be evaluated on the two arms using a Kaplan-Meir curve and compared using a log-rank test.
Time Frame
through day 113
Title
Quality of Life (QOL)
Description
QOL factors in the PRO surveys will be measured using T-scores and T-tests or ANOVA.
Time Frame
baseline, day 43 and day 113
Title
Objective Response Rate (ORR)
Description
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
Time Frame
through day 113
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA:
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%).
The ability of the subject to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
Participants who are receiving any investigational agents other than relatlimab or nivolumab
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
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Katherine O Lee-Wisdom, R.N.
Phone
(240) 858-3525
Email
katherine.lee-wisdom@nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
James L Gulley, M.D.
Phone
(301) 480-7164
Email
gulleyj@mail.nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James L Gulley, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
Phone
888-624-1937
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
.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.
IPD Sharing Time Frame
Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active
IPD Sharing Access Criteria
Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_000251-C.html
Description
NIH Clinical Center Detailed Web Page
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The Effect of Diet and Exercise on ImmuNotherapy and the Microbiome (EDEN)
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