The Impact of Dietary Protein on the Metabolome
Condition: Diet, Healthy
Study type: Interventional

Summary: 
      It is known that tumors have an affinity for taking up amino acids from circulation or nearby
      tissues to use as a fuel source, to enhance their growth. Work in rodents has shown that when
      the levels of amino acids are reduced in diet, tumor growth is slowed and tumors are more
      susceptible to anti-cancer therapies. There are limited evidence-based dietary
      recommendations for cancer patients, which represents an urgent and unmet need. It is likely
      that reducing dietary protein will be beneficial, however this has not been tested. In
      advance of carrying out a study in cancer patients a study in healthy volunteers needs to be
      conducted to determine whether altering the amount of dietary protein, impacts the levels of
      amino acids (or other metabolites) in blood or the intestine. By demonstrating that altering
      dietary protein can alter the metabolome of healthy individuals, it will provide the
      information needed to reduce protein intake in cancer patients in future studies.
    

Detailed description: 
      After providing consent, subjects will undergo an indirect calorimetry test, which involves
      breathing through a disposable, single-use mouth piece into a machine that estimates calorie
      needs based on oxygen consumed and CO2 produced. Then subjects will be instructed on how to
      keep a 3-day food record and complete the Qualtrics survey designed for this purpose within 2
      weeks of consenting. Nutrient content of the participants' typical diet will be calculated,
      based on the 3-day and Qualtrics-based food/beverage log, using Food Processor software.
      Meals for the acclimation period will be created to mimic the participants' typical diet
      (daily calories and percent of calories from carbohydrate, protein and fat), as well as to
      meet their calorie needs per the indirect calorimeter test, for the first 7-9 days of the
      study. High protein diets (2g of protein/kg/day) will then be devised and provided for the
      next 14-16 days. Following this period, reduced protein diets (0.8g of protein/kg/day) will
      be devised and provided for the next 14-16 days. Fat content will be modulated to keep diets
      isocaloric while keeping carbohydrate content stable. Participants will choose between two
      3-day cycle menus for each feeding phase. Meals will be prepared in a metabolic kitchen
      housed in SBU's Business Incubator at Calverton. Meals will be prepared in batches, packaged
      and frozen at the incubator, then transported in a cooler with thermometers to the Food
      Service Department at SBU Hospital. Meals will be kept frozen in freezers until the day they
      are provided to participants. Logs of temperatures of coolers will be maintained daily, with
      temperatures checked every hour.

      In order to provide meals, participants will come to the feeding site to eat breakfast onsite
      and pick up other meals and snacks for the rest of the day. Participants will be provided a
      closed envelope containing a form that will list their participant ID# and age in which
      they'll sign in and indicate if they've begun any new medications or been diagnosed with a
      disease since starting the study. Additionally, twice per week, participants will be weighed
      using a digital scale in order to track changes in body weight while on the study. If weight
      changes greater than 2% of baseline, calorie content of the meals will be modified to avoid
      further weight changes. Food for the rest of the day will be provided in an insulated bag
      containing frozen cold packs and participants will be instructed to keep lunch and dinner in
      the insulated bag or a refrigerator until eaten. They will be instructed to heat the
      respective meals in a microwave until hot, prior to consumption. They will be instructed to
      take a picture of each meal before and after eating and upload the pictures via a
      Qualtrics-based survey, in order for the investigators to estimate how much food has been
      eaten at each meal. Although participants will be instructed to only eat the food and
      beverages provided for the study, they will log any consumption of food or beverages not
      provided for the study via this same Qualtrics-based survey. Consumption of water, black
      coffee and tea will not be logged.

      During days 7-9, 24-26 and 41-43 participants will provide a stool sample to be placed into a
      sterile container (provided by the study team) then placed into an opaque brown paper bag and
      provided to the study team. At the same time the stool sample is delivered, blood will be
      drawn to generate serum. If a participant provides samples in the earlier part of the
      collection period (e.g. day 7) they will proceed immediately to the next phase of the study.
    

Intervention name(s): Dietary protein
Intervention type(s): Other
Intervention description(s): High protein followed by reduced protein diet
Intervention model: Sequential Assignment
Intervention model description: Longitudinal
Masking: None (Open Label)
Primary purpose: Basic Science