Effects of Alpha-lactalbumin Intake on Metabolic and Cognitive Functions in Elderly
Primary Purpose
Mild Cognitive Impairment
Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Alpha-lactalbumin
Whey
Casein
Sponsored by
About this trial
This is an interventional supportive care trial for Mild Cognitive Impairment focused on measuring Mild cognitive impairment, Protein digestion, Tryptophan digestion, Cognitive function, Mood, Muscle function, Alpha-lactalbumin
Eligibility Criteria
Inclusion criteria subjects with dementia:
- Dementia diagnosis
- Ability to walk, sit down and stand up independently
- Age 55 years or older
- Ability to lie in supine or elevated position for 8 hours
- Willingness and ability to comply with the protocol, including:
Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit
Inclusion criteria healthy subjects:
- Healthy male or female according to the investigator's or appointed staff's judgment
- Ability to walk, sit down and stand up independently
- Age 55 years or older
- Ability to lie in supine or elevated position for 8 hours
- Willingness and ability to comply with the protocol, including:
Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit
Exclusion Criteria:
- Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (for healthy control group only)
- Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
- Indication of severe cognitive impairment (MOCA score < 17)
- Established diagnosis of Insulin Dependent Diabetes Mellitus
- History of untreated metabolic disease(s) including hepatic or renal disorder
- Presence of acute illness or metabolically unstable chronic illness
- Presence of fever within the last 3 days
- Preplanned surgery of procedures that would interfere with the conduct of the study
- Any other condition according to the PI or study physician that would interfere with proper conduct of the study / safety of the patient
- Current alcohol or drug abuse
- Known allergy to milk or milk products
- Use of long-term oral corticosteroids or short course of oral corticosteroids 4 weeks preceding first test day
- Use of protein or amino acid containing nutritional supplements within 5 days of test day
- (Possible) pregnancy
- BMI of < 18.5 or ≥ 40 kg/m2
- Dietary or lifestyle characteristics: When during the period from enrollment to completion of the study (end of test day) any condition is developed, whether causing the subject to not meet inclusion criteria or to meet exclusion criteria, the subject will be excluded from the study
Sites / Locations
- Texas A&M University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Healthy
MCI
Dementia
Arm Description
healthy control subjects
mild cognitive impariments
established diagnosis of dementia
Outcomes
Primary Outcome Measures
Net whole-body protein synthesis
Change in whole-body protein synthesis rate after intake of meal
Secondary Outcome Measures
Citrulline rate of appearance
Plasma enrichment of citrulline
Skeletal and respiratory muscle strength
Difference in leg strength and fatigue, handgrip strength and fatigue, and inspiratory and expiratory pressure between older adults with and without MCI.
Cognitive function and mood
Outcome of neuro-psychological tests in healthy older adults with and without MCI in relation to the tryptophan metabolism
Protein digestion after feeding
Ratio enrichment free phenylalanine versus phenylalanine from protein spirulina
Arginine turnover rate
Arginine enrichment in plasma
Whole body collagen breakdown rate
Hydroxyproline enrichment in plasma
Tryptophan turnover rate
Tryptophan enrichment in plasma in postabsorptive state and after intake of meal
Insulin response to feeding
Acute change from postabsorptive state after intake of meal
Fat-free mass
Characteristics of study subjects
Myofibrillar protein breakdown rate
3methylhistidine enrichment in plasma
Glycine rate of appearance
Glycine enrichment in plasma
Taurine turnover rate
Enrichment of taurine in plasma
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02082418
Brief Title
Effects of Alpha-lactalbumin Intake on Metabolic and Cognitive Functions in Elderly
Official Title
Effects of Alpha-lactalbumin on Metabolic and Cognitive Functions in Healthy Older Adults
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Unknown status
Study Start Date
March 2014 (undefined)
Primary Completion Date
February 2020 (Anticipated)
Study Completion Date
February 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Texas A&M University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Aging modifies the metabolic pathway of the neurotransmitter serotonin by reducing the synthesis rate and increasing the breakdown rate of serotonin, possibly related to the observed enhanced sensitivity of the serotonergic pathway. Since serotonin plays a prominent role in neuropsychological functions such as anxiety, mood and memory, the enhanced sensitivity of the serotonergic pathway in aging can probably explain the fact that elderly are more vulnerable to develop cognitive deficits and depressive symptoms.
Serotonin synthesis in brain is regulated by its precursor tryptophan (TRP). Because tryptophan is an essential amino acid, modifying the availability of tryptophan through dietary intake, can directly influence central serotonin metabolism and consequently affective and cognitive processes.
The aim of this study is to test the hypothesis that an acute intake of whey protein with high levels of TRP such as alpha-lactalbumin can stabilize the metabolism of serotonin and subsequently enhance metabolic and cognitive functions in healthy older adults. The acute effects of this dietary protein will be investigated in subjects with mild cognitive impairment (MCI), or dementia, compared to control subjects in order to examine whether healthy older subject with MCI benefit more from the intake of alpha-lactalbumin and/or whey. The investigators will investigate if this meal can optimize serotonin metabolism by elevating plasma TRP levels and plasma TRP appearance and enhance splanchnic TRP extraction. In addition, the effects on mood and cognitive functions will be examined.
Detailed Description
The study involves for all subjects 3 test days (approximately 8 hours each). On this test day the investigators will examine the acute effects of a protein meal. Subjects will receive a mixture of alpha-lactalbumin and/or whey and/or casein, carbohydrates and amino acid stable isotopes to investigate protein and amino acid kinetics (assigned to alpha-lactalbumin or whey or casein group on test day 1, then switch on test day 2 and 3). The subjects will receive these stable isotopes by infusion in their blood and by oral intake (e.g. simultaneously with protein meal). For study purposes, blood will be drawn approx. 25 times during 8 hours on the test day, altogether about 100-120 ml of blood will be drawn on the test day.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment
Keywords
Mild cognitive impairment, Protein digestion, Tryptophan digestion, Cognitive function, Mood, Muscle function, Alpha-lactalbumin
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Healthy
Arm Type
Experimental
Arm Description
healthy control subjects
Arm Title
MCI
Arm Type
Experimental
Arm Description
mild cognitive impariments
Arm Title
Dementia
Arm Type
Experimental
Arm Description
established diagnosis of dementia
Intervention Type
Dietary Supplement
Intervention Name(s)
Alpha-lactalbumin
Intervention Description
Subjects will ingest the liquid meal containing alpha-lactalbumin and carbohydrates (0.6 g/kg FFM protein + 0.3 g/kg FFM carbohydrates).
Intervention Type
Dietary Supplement
Intervention Name(s)
Whey
Intervention Description
commercially available whey protein
Intervention Type
Dietary Supplement
Intervention Name(s)
Casein
Intervention Description
commercially available casein protein
Primary Outcome Measure Information:
Title
Net whole-body protein synthesis
Description
Change in whole-body protein synthesis rate after intake of meal
Time Frame
0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Secondary Outcome Measure Information:
Title
Citrulline rate of appearance
Description
Plasma enrichment of citrulline
Time Frame
Postabsorptive state during 2 hours
Title
Skeletal and respiratory muscle strength
Description
Difference in leg strength and fatigue, handgrip strength and fatigue, and inspiratory and expiratory pressure between older adults with and without MCI.
Time Frame
1 day
Title
Cognitive function and mood
Description
Outcome of neuro-psychological tests in healthy older adults with and without MCI in relation to the tryptophan metabolism
Time Frame
Postabsorptive state during 3 hours and change after feeding
Title
Protein digestion after feeding
Description
Ratio enrichment free phenylalanine versus phenylalanine from protein spirulina
Time Frame
0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Title
Arginine turnover rate
Description
Arginine enrichment in plasma
Time Frame
Postabsorptive state during 3 hours
Title
Whole body collagen breakdown rate
Description
Hydroxyproline enrichment in plasma
Time Frame
Postabsorptive state during 3 hours
Title
Tryptophan turnover rate
Description
Tryptophan enrichment in plasma in postabsorptive state and after intake of meal
Time Frame
Postabsorptive state during 3 hours and change after feeding
Title
Insulin response to feeding
Description
Acute change from postabsorptive state after intake of meal
Time Frame
During 3 hours after feeding
Title
Fat-free mass
Description
Characteristics of study subjects
Time Frame
Postabsorptive state during 15 min
Title
Myofibrillar protein breakdown rate
Description
3methylhistidine enrichment in plasma
Time Frame
0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
Title
Glycine rate of appearance
Description
Glycine enrichment in plasma
Time Frame
Postabsorptive state during 3 hours
Title
Taurine turnover rate
Description
Enrichment of taurine in plasma
Time Frame
Postabsorptive state during 3 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria subjects with dementia:
Dementia diagnosis
Ability to walk, sit down and stand up independently
Age 55 years or older
Ability to lie in supine or elevated position for 8 hours
Willingness and ability to comply with the protocol, including:
Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit
Inclusion criteria healthy subjects:
Healthy male or female according to the investigator's or appointed staff's judgment
Ability to walk, sit down and stand up independently
Age 55 years or older
Ability to lie in supine or elevated position for 8 hours
Willingness and ability to comply with the protocol, including:
Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit
Exclusion Criteria:
Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (for healthy control group only)
Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
Indication of severe cognitive impairment (MOCA score < 17)
Established diagnosis of Insulin Dependent Diabetes Mellitus
History of untreated metabolic disease(s) including hepatic or renal disorder
Presence of acute illness or metabolically unstable chronic illness
Presence of fever within the last 3 days
Preplanned surgery of procedures that would interfere with the conduct of the study
Any other condition according to the PI or study physician that would interfere with proper conduct of the study / safety of the patient
Current alcohol or drug abuse
Known allergy to milk or milk products
Use of long-term oral corticosteroids or short course of oral corticosteroids 4 weeks preceding first test day
Use of protein or amino acid containing nutritional supplements within 5 days of test day
(Possible) pregnancy
BMI of < 18.5 or ≥ 40 kg/m2
Dietary or lifestyle characteristics: When during the period from enrollment to completion of the study (end of test day) any condition is developed, whether causing the subject to not meet inclusion criteria or to meet exclusion criteria, the subject will be excluded from the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marielle P Engelen, PhD
Organizational Affiliation
Texas A&M University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Texas A&M University
City
College Station
State/Province
Texas
ZIP/Postal Code
77843
Country
United States
12. IPD Sharing Statement
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Effects of Alpha-lactalbumin Intake on Metabolic and Cognitive Functions in Elderly
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