Anabolic Response Cancer

Cancer Clinical Trial

Official title:

Assessment of Anabolic Responsiveness to Protein Intake in Advanced Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02793531
• Other study ID #: IRB2015-0460
• Status: Withdrawn
• Phase: N/A
• First received: May 24, 2016
• Last updated: March 20, 2018
• Start date: May 2016
• Est. completion date: May 2019

Study information

• Verified date: March 2018
• Source: Texas A&M University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2019
• Est. primary completion date: May 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer

Intervention

Other:
• Stable isotope amino acid infusion
such as glycerol, D2O, tyrosine, phenylalanine, glucose, arginine, and citrulline

Locations

Country	Name	City	State
United States	Texas A&M University-CTRAL	College Station	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Texas A&M University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in net whole-body protein synthesis	Change in whole-body protein synthesis rate after intake of meal	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
Secondary	Body Composition	Body composition as measured by Dual-Energy X-ray Absorptiometry	15 minutes on screening or study day 1
Secondary	Skeletal muscle strength	handgrip	on study day 1
Secondary	Skeletal muscle strength	kin-com 1-leg test	on study day 1
Secondary	Respiratory muscle strength	Maximum inhalation and exhalation pressure	on study day 1
Secondary	Gut function	Digestion of the stable tracers of amino acid	In postabsorptive and prandial state every 20 minutes up to 6 hours before each sip feeding on study day
Secondary	Group differences in state of mood as measured by the Hospital Anxiety and Depression Scale (HADS)	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.	Postabsorptive state during 3 hours and change after feeding on study day 1
Secondary	Group differences in activity as measured by Physical Activity Scale for the Elderly (PASE)	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.	Postabsorptive state during 3 hours and change after feeding on study day 1
Secondary	Group differences in state of mood as measured by the Profile of Mood State (POMS)	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.	Postabsorptive state during 3 hours and change after feeding on study day 1
Secondary	appetite questionnaire	The subject is asked to rate various aspects of their appetite as relates to overall health	study day 1
Secondary	Group differences in attention and executive functions as measured by Stroop Color-Word Test (SCWT)	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.	Postabsorptive state during 3 hours and change after feeding on study day 1]
Secondary	Group differences in learning and memory as measured by Controlled Oral Word Association Test (COWAT)	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.	Postabsorptive state during 3 hours and change after feeding on study day 1
Secondary	Group differences in overall cognitive abilities as measured by Montreal Cognitive Assessment (MoCA)	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.	Postabsorptive state during 3 hours and change after feeding on study day 1
Secondary	Group differences in attention and executive functions as measured by Brief-A	a standardized self-report that captures views of an adult's executive functions or self-regulation in his or her everyday environment.	Postabsorptive state during 3 hours and change after feeding on study day 1
Secondary	diet recall	The subject is asked to recall in detail all the food and drink consumed during the 24 hours prior to the test day.	Postabsorptive state during 3 hours and change after feeding on study day 1
Secondary	Group differences in attention and executive functions as measured by Trail Making Test (TMT)	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.	Postabsorptive state during 3 hours and change after feeding on study day 1
Secondary	Functional Status	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%.	Postabsorptive state during 3 hours and change after feeding on study day 1
Secondary	Group differences in learning and memory as measured by Auditory Verbal Learning Test (AVLT)	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.	Postabsorptive state during 3 hours and change after feeding on study day 1