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Anabolic Response Cancer

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ClinicalTrials.gov Identifier: NCT02793531
Recruitment Status : Withdrawn (low enrollment potential in local community)
First Posted : June 8, 2016
Last Update Posted : March 22, 2018
Sponsor:
Information provided by (Responsible Party):
Marielle PKJ Engelen, PhD, Texas A&M University

Tracking Information
First Submitted Date  ICMJE May 24, 2016
First Posted Date  ICMJE June 8, 2016
Last Update Posted Date March 22, 2018
Study Start Date  ICMJE May 2016
Estimated Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2016)
Change in net whole-body protein synthesis [ Time Frame: 0, 2, 5, 10, 15, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 225, 240, 260, 280, 300, 320, 340, 360 ± 5 min ]
Change in whole-body protein synthesis rate after intake of meal
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2016)
  • Body Composition [ Time Frame: 15 minutes on screening or study day 1 ]
    Body composition as measured by Dual-Energy X-ray Absorptiometry
  • Skeletal muscle strength [ Time Frame: on study day 1 ]
    handgrip
  • Skeletal muscle strength [ Time Frame: on study day 1 ]
    kin-com 1-leg test
  • Respiratory muscle strength [ Time Frame: on study day 1 ]
    Maximum inhalation and exhalation pressure
  • Gut function [ Time Frame: In postabsorptive and prandial state every 20 minutes up to 6 hours before each sip feeding on study day ]
    Digestion of the stable tracers of amino acid
  • Group differences in state of mood as measured by the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Postabsorptive state during 3 hours and change after feeding on study day 1 ]
    a fourteen item self-assessment scale. Seven of the items related to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression.
  • Group differences in activity as measured by Physical Activity Scale for the Elderly (PASE) [ Time Frame: Postabsorptive state during 3 hours and change after feeding on study day 1 ]
    questionnaire is intended for use in an elderly population and focuses on 3 types of activities: leisure time activities, household activities and work-related activities.
  • Group differences in state of mood as measured by the Profile of Mood State (POMS) [ Time Frame: Postabsorptive state during 3 hours and change after feeding on study day 1 ]
    A psychological distress scale to measure mood disturbance in 6 domains - fatigue-inertia, vigor-activity, tension-anxiety, depression-dejection, anger-hostility, and confusion-bewilderment. Healthy populations take 3 to 7 minutes to complete, and others may take up a bit longer.
  • appetite questionnaire [ Time Frame: study day 1 ]
    The subject is asked to rate various aspects of their appetite as relates to overall health
  • Group differences in attention and executive functions as measured by Stroop Color-Word Test (SCWT) [ Time Frame: Postabsorptive state during 3 hours and change after feeding on study day 1] ]
    a word page with words printed in black ink, a color page with blocks printed in color, and a color-word page where the color and the word do not match. The examinee reads the words or names the ink colors as quickly as possible within a time limit. Measures selective attention and inhibitory control. The total time in seconds was reported for each trial.
  • Group differences in learning and memory as measured by Controlled Oral Word Association Test (COWAT) [ Time Frame: Postabsorptive state during 3 hours and change after feeding on study day 1 ]
    The examinee is required to say as many words as they can think of in one minute that begin with a given letter of the alphabet. The task contains three trials. Measures phonetic verbal fluency. The raw score (total and mean words recorded across the three trials) was reported.
  • Group differences in overall cognitive abilities as measured by Montreal Cognitive Assessment (MoCA) [ Time Frame: Postabsorptive state during 3 hours and change after feeding on study day 1 ]
    assesses several cognitive domains and is used for the screening of mild cognitive impairment. Total scores range from 0-30 with lower scores indicating decreased functioning.
  • Group differences in attention and executive functions as measured by Brief-A [ Time Frame: Postabsorptive state during 3 hours and change after feeding on study day 1 ]
    a standardized self-report that captures views of an adult's executive functions or self-regulation in his or her everyday environment.
  • diet recall [ Time Frame: Postabsorptive state during 3 hours and change after feeding on study day 1 ]
    The subject is asked to recall in detail all the food and drink consumed during the 24 hours prior to the test day.
  • Group differences in attention and executive functions as measured by Trail Making Test (TMT) [ Time Frame: Postabsorptive state during 3 hours and change after feeding on study day 1 ]
    Part A, the examinee is instructed to connect a set of 25 circles with numbers as quickly as possible while maintaining accuracy. In Part B, the examinee is instructed to connect a set of 25 circles, alternating between numbers and letters, as quickly as possible while maintaining accuracy. Measures attentional resources and is a measure of the frontal lobe "executive" functions of visual search, set-switching and mental flexibility. The total time in seconds was reported for each measure.
  • Functional Status [ Time Frame: Postabsorptive state during 3 hours and change after feeding on study day 1 ]
    Functional status will be assessed by the Karnofsky Performance Score, a widely used method to assess the functional status of a cancer patient. It describes a patient's functional status as a comprehensive 11-point scale ranging from 0% to 100%.
  • Group differences in learning and memory as measured by Auditory Verbal Learning Test (AVLT) [ Time Frame: Postabsorptive state during 3 hours and change after feeding on study day 1 ]
    a verbal episodic memory test that evaluates a wide diversity of functions: short-term auditory-verbal memory, rate of learning, retention and recognition of information.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anabolic Response Cancer
Official Title  ICMJE Assessment of Anabolic Responsiveness to Protein Intake in Advanced Cancer
Brief Summary

Weight loss and muscle wasting commonly occurs in patients with cancer, negatively influencing their quality of life, treatment response and survival. Weight changes in patients with cancer may be the consequence of energy imbalance and disturbances in protein metabolism, poor treatment tolerance, hormonal alterations, systemic inflammation etc. This results in body composition modifications in favor of fat gain and/or lean body mass loss in early stage cancer. However, in advanced cancer mostly loss of both fat mass and lean mass has been found.

Unfortunately, gains in muscle mass are difficult to achieve. In a previous study of the Investigators, a bolus (15 g) of an essential amino acid mixture as present in milk protein was able to stimulate whole-body protein anabolism equally and effectively in weight-losing patients with lung cancer. This indicates the high potential of proteins with high essential amino acids as therapeutic agents to increase muscle mass in these patients. However, the dose-response effect to reach optimal whole-body protein anabolism is yet unknown and can differ among patients. Therefore, the Investigators would like to study the effects of several dosages of a protein with high essential amino acid levels, administered by sip feeding, on whole-body protein anabolism in patients with cancer in comparison with healthy older adults. Furthermore, the individual protein requirements of cancer patients may be established as this is the cornerstone of nutritional support. Specifically to establish 'the anabolic threshold', when protein breakdown equals synthesis and the response and the relation between protein intake and net protein synthesis are critical.

Detailed Description

In this study, the Investigators will test the following hypothesis: A protein meal with high EAA levels will stimulate protein anabolism in a dose-dependent way but the exact relationship differs among cancer patients. The primary endpoint will be the extent of stimulation of net whole-body protein synthesis at each level of protein intake in the individual cancer and control subject. This project will provide important clinical information on the anabolic capacity of dietary protein with high EAA levels and the level of protein intake required to become anabolic in cancer patients on an individual bases. In this way, this study will provide preliminary data for the development of individualized nutritional strategies that will stop the process of ongoing muscle loss in cancer patients.

General aims:

  • To study the whole-body protein anabolic effect of several dosages of a high-quality protein sip feeding in cancer subjects as compared to healthy controls.
  • To investigate the anabolic threshold in subjects with cancer as compared to healthy controls.

The mechanisms underlying lean tissue loss in cancer remain to be unraveled, which may be because of the complexity of the metabolic alterations that are present when symptoms such as weight loss become obvious. Multiple factors like anorexia and inflammation are present in cancer, all contributing to the loss of lean tissue in these patients by creating a drain on the body protein stores. Previous studies showed that oral supplementation of large amounts of calories in cancer is only partially successful and this indicates that the composition of dietary supplements and meals is important to successfully counteract muscle wasting. Although our previous study supports the concept of supplementing high-quality milk proteins in lung cancer subjects, the dose-response anabolic effects of proteins with high EAA levels are still unclear. Furthermore, there is no insight in the actual protein requirements in cancer. The knowledge gained from this study will benefit our insight in terms of promotion of protein gain after feeding in cancer patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE Cancer
Intervention  ICMJE Other: Stable isotope amino acid infusion
such as glycerol, D2O, tyrosine, phenylalanine, glucose, arginine, and citrulline
Study Arms  ICMJE
  • Experimental: Healthy matched controls

    screening visit: body weight and composition by DXA, height, and vital signs will be assessed. Subjects may sign a medical release form to obtain medical and psychological information about them that will help determine study eligibility or can be used for later coding.

    study day: muscle mass and function tests, resting energy expenditure, stable isotope infusions with blood draws, and questionnaires regarding quality of life, mood and depression, diet.

    Intervention: Other: Stable isotope amino acid infusion
  • Experimental: Cancer subjects

    screening visit: body weight and composition by DXA, height, and vital signs will be assessed. Subjects may sign a medical release form to obtain medical and psychological information about them that will help determine study eligibility or can be used for later coding.

    study day: muscle mass and function tests, resting energy expenditure, stable isotope infusions with blood draws, and questionnaires regarding quality of life, mood and depression, diet.

    Intervention: Other: Stable isotope amino acid infusion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: March 20, 2018)
0
Original Estimated Enrollment  ICMJE
 (submitted: June 3, 2016)
60
Estimated Study Completion Date  ICMJE May 2019
Estimated Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria cancer subjects:

  • Age 18 years or older
  • Ability to lie in supine or elevated position for 8 hours
  • Diagnosed with stage III/IV cancer (all solid tumors excluding breast or prostate)
  • No chemotherapy/radiotherapy within past month prior to the study day
  • Willingness and ability to comply with the protocol

Inclusion criteria healthy subjects:

  • Healthy male or female according to the investigator's or appointed staff's judgment
  • Age 18 years or older
  • Ability to lay in supine or elevated position for 8 hours
  • No diagnosis of cancer
  • No diagnosis of diabetes
  • Willingness and ability to comply with the protocol

Exclusion Criteria all subjects:

  • Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (for healthy control group only)
  • Presence of fever within the last 3 days
  • Untreated metabolic diseases including hepatic or renal disorder
  • Presence of acute illness or metabolically unstable chronic illness
  • BMI of < 18.5 or ≥ 35 kg/m2 (for healthy control group only)
  • Dietary or lifestyle characteristics: Current alcohol or drug abuse, Use of protein or amino acid containing nutritional supplements within 5 days prior to the study day
  • Known allergy to milk or milk products
  • Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
  • (Possible) pregnancy
  • Any other condition according to the PI or nurse that was found during the screening visit, that would interfere with the study or safety of the patient
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02793531
Other Study ID Numbers  ICMJE IRB2015-0460
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Marielle PKJ Engelen, PhD, Texas A&M University
Study Sponsor  ICMJE Texas A&M University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Texas A&M University
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP