Ignite Creation Date:
2024-05-06 @ 3:59 PM
Last Modification Date:
2024-10-26 @ 2:01 PM
Study NCT ID:
NCT04831203
Status:
COMPLETED
Last Update Posted:
2022-11-09
First Post:
2021-04-01
Brief Title:
NWT-03 and Brain Function
Sponsor:
Maastricht University Medical Center
Organization:
Maastricht University Medical Center
Study Overview
Official Title:
An Egg-protein Hydrolysate NWT-03 to Boost Brain Function - Mind Your Blood Vessels
Status:
COMPLETED
Status Verified Date:
2022-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Age-related chronic diseases including dementia type II diabetes mellitus T2DM and cardiovascular disease CVD become more prevalent and of increasing societal concern Common denominators of these co-morbidities are insulin-resistance and impaired vascular function Animal and short-term human studies now suggest that NWT-03 - an egg-protein hydrolysate - improves insulin-sensitivity and peripheral vascular function which are risk markers for the development of T2DM and CVD Insulin-resistance is also associated with cognitive decline while impaired brain vascular function is an important event preceding the development of impaired cognitive performance The investigators have already shown in a shorter-term trial 12 weeks beneficial effects of a daily dose of 50 g of NWT-03 on cognitive performance However underlying mechanisms have not yet been addressed while the long-term effects remain unknown Thus the investigators now hypothesize that NWT-03 beneficially affects cognitive performance and brain vascular function following long-term daily intake
The primary objectives of this trial are to evaluate in overweight or obese adults aged 60-75 with subjective cognitive decline SCD the effects of a 36-weeks NWT-03 intervention on 1 cognitive performance using a neurophysiological test battery and 2 cerebral blood flow as quantified by the current non-invasive gold standard magnetic resonance imaging MRI perfusion method Arterial Spin Labeling ASL Secondary study objectives are to examine effects on insulin-sensitivity and peripheral vascular function
This intervention study will have a randomized controlled parallel design The total study duration will be 36 weeks Forty-four older adults aged 60-75 years with a Body Mass Index BMI between 25-35 kgm2 overweight or obese and subjective cognitive decline SCD as assessed with the cognitive failure questionnaire will participate These study individuals are known to be at increased risk of cognitive impairment allowing for improvement by the intervention During the study subjects will receive daily in the morning 50 g NWT-03 or placebo powders for 36 weeks
The primary objectives of this trial are to evaluate in overweight or obese adults aged 60-75 with subjective cognitive decline SCD the effects of a 36-weeks NWT-03 intervention on 1 cognitive performance using a neurophysiological test battery and 2 cerebral blood flow as quantified by the current non-invasive gold standard magnetic resonance imaging MRI perfusion method Arterial Spin Labeling ASL Secondary study objectives are to examine effects on insulin-sensitivity and peripheral vascular function
This intervention study will have a randomized controlled parallel design The total study duration will be 36 weeks Forty-four older adults aged 60-75 years with a Body Mass Index BMI between 25-35 kgm2 overweight or obese and subjective cognitive decline SCD as assessed with the cognitive failure questionnaire will participate These study individuals are known to be at increased risk of cognitive impairment allowing for improvement by the intervention During the study subjects will receive daily in the morning 50 g NWT-03 or placebo powders for 36 weeks
Detailed Description:
Due to the aging population the number of people with cognitive impairment will have doubled by the year 2035 Also the number of individuals with type-2 diabetes mellitus T2DM and cardiovascular disease CVD will have increased substantially Common denominators of these age-related co-morbidities in humans are insulin-resistance and an impaired vascular function
Newtricious NWT-03 is a novel dietary egg-protein hydrolysate that has proven benefits on glucose and insulin metabolism as the investigators have recently shown in overweight or obese individuals with T2DM or impaired glucose tolerance Furthermore peripheral vascular function was improved The potential explanation of these effects may arise from the finding that NWT-03 blocks the enzyme dipeptidyl peptidase DPP-IV 7 - a pharmaceutical target for the treatment of T2DM and CVD - that beneficially affects insulin metabolism Compared to the wealth of knowledge about the impact of insulin-sensitivity and peripheral vascular function on the risk of T2DM and CVD emerging evidence also indicates that these risk markers affect cognitive performance This is of great interest since the brain is an insulin sensitive organ and insulin-resistance is associated with cognitive decline while impaired brain vascular function is a key pathophysiological event preceding the development of an impaired cognitive performance A study in mice also showed effects of NWT-03 on neuro-inflammation and oxidative stress in the brain In fact a decreased expression of TNF-α and improved expression of enzymes involved in anti-oxidative processes were observed The investigators have also shown in a similar - but shorter-term 12 weeks - trial beneficial effects of NWT-03 on executive function as the latency of response was reduced manuscripts in preparation In addition the hen egg-white hydrolysate ie LumiVida also improved reaction time in middle-aged women Underlying mechanisms of these hydrolysates on cognitive performance were however not addressed In our review the investigators summarized the impact of dietary factors and exercise on brain vascular function in adults and discussed the relation between these effects with changes in cognitive performance It was concluded that studies on the longer-term effects of lifestyle factors including diet and physical exercise can improve brain vascular function which may contribute to the beneficial effects observed on cognitive performance In addition longer-term effects remain unknown and only a limited number of parameters related to cognitive performance were studied Therefore the investigators propose to perform a long-term placebo-controlled double blind intervention study including functional outcome parameters and study in vivo effects of NWT-03 on brain vascular function which is a potential target to prevent or slow-down cognitive impairments and improve cognitive performance Focus will be on older adults aged 60-75 years with a Body Mass Index BMI between 25-35 kgm2 overweight or obese and subjective cognitive decline SCD as assessed with the cognitive failure questionnaire These individuals are known to be at increased risk of cognitive impairment allowing for improvement by the intervention
Secondary study endpoints are effects on insulin-sensitivity and peripheral vascular function which are risk markers that may affect cognitive performance Finally the investigators will focus on other potential mechanisms underlying effects on brain function ie ambulatory blood pressure structural brain status humoral factors and the more conventional cardiometabolic risk markers and other perceivable benefits including general well-being quality of life sleep characteristics and mood and physical fitness
Effects will be investigated using innovative and emerging non-invasive brain magnetic resonance imaging MRI-perfusion methods while focusing on whole brain and cognitive-control brain areas plus cognitive performance tests Furthermore the investigators have reviewed that cerebral blood flow in gray matter is a sensitive and straightforward marker of brain vascular function which correlates with cognitive performance Of note lower cerebral blood flow is associated with accelerated cognitive decline and increased risk of dementia in the general population based on results of the Rotterdam prospective cohort study Cerebral blood flow changes will be quantified on a Siemens 3 Tesla Magnetom Prisma Fit scanner at the Scannexus research facilities by the non-invasive gold standard approach the MRI perfusion method pseudo-continuous Arterial Spin LabelingCognitive performance will be assessed using CANTAB ie Cambridge Neuropsychological Test Automated Battery These validated assessments for state-of-the-art cognitive testing focus on the main cognitive domains ie executive function attention and memory Brain vascular function will be investigated using innovative and emerging non-invasive brain magnetic resonance imaging MRI-perfusion methods while focusing on whole brain and cognitive-control brain areas plus cognitive performance tests Furthermore the investigators have reviewed that cerebral blood flow in gray matter is a sensitive and straightforward marker of brain vascular function which correlates with cognitive performance Of note lower cerebral blood flow is associated with accelerated cognitive decline and increased risk of dementia in the general population based on results of the Rotterdam prospective cohort study Cerebral blood flow changes will be quantified on a Siemens 3 Tesla Magnetom Prisma Fit scanner at the Scannexus research facilities by the non-invasive gold standard approach the MRI perfusion method pseudo-continuous Arterial Spin Labeling
Considering the background information given in the previous paragraph the following research questions are formulated
Primary research question
What are the effects in older adults with a BMI between 25-35 kgm2 and SCD of a 36-weeks NWT-03 intervention on i cognitive performance using a neurophysiological test battery and ii cerebral blood flow as quantified by the MRI-perfusion method Arterial Spin Labelling
Major null hypotheses H0
1 A 36-weeks NWT-03 intervention does not significantly affect cognitive performance in older adults with a BMI between 25-35 kgm2 and SCD
2 A 36-weeks NWT-03 intervention does not significantly affect cerebral blood flow as assessed by Arterial Spin Labelling in older adults with a BMI between 25-35 kgm2 and SCD
Major alternate hypotheses Ha
1 A 36-weeks NWT-03 intervention significantly affects cognitive performance in older adults with a BMI between 25-35 kgm2 and SCD
2 A 36-weeks NWT-03 intervention significantly affects cerebral blood flow as assessed by Arterial Spin Labelling in older adults with a BMI between 25-35 kgm2 and SCD
Secondary research question
What are the effects in older adults with SCD of a 36-weeks NWT-03 intervention on insulin sensitivity and peripheral vascular function which are risk markers for T2DM and CVD
Exploratory research questions
What are the effects in older adults with subjective cognitive decline SCD of a 36-weeks NWT-03 intervention on
mechanisms underlying effects on brain function including structural brain status humoral factors and the more conventional cardiometabolic risk markers
perceivable consumer benefits including physical fitness and general well-being
A randomized placebo-controlled trial with a parallel design will be conducted
Before screening subjects will be informed about the procedures and informed consent will be obtained Following screening study participants that fulfill all inclusion criteria and are willing to participate will be asked to participate in this study
Subjects will be informed about their screening results including anthropometric measures weight length body mass index systolic and diastolic blood pressure SBP and DBP serum total cholesterol and triacylglycerol concentrations and plasma glucose concentrations When treatment with drugs or lifestyle interventions is indicated according to the Standards of the Dutch general practitioners community NHG subjects will be advised to consult their general practitioner Study results obtained during the intervention trial ie brain vascular function will be reported in a descriptive way at a group level for example brain vascular function is improved because no accepted normal ranges exist for these measurements
On the days before blood sampling adults are asked not to perform any strenuous physical exercise or to consume alcoholic beverages On the morning of blood sampling - after a 12-hour overnight fast from 800 PM - study subjects are only allowed to drink a glass of water Subjects are also asked not to change their habitual diet during the study Finally subjects are asked to come to the Metabolic Research Unit MRUM by public transport or car and not by foot or bike to standardize research measurements as much as possible
At baseline and after 18 weeks anthropometric measurements will be performed and a fasting blood sample will be drawn At baseline and after 36 weeks subjects have to attend two times the research facilities to perform the follow-up measurements once for the Day A measurements and once for the Day B measurements During these tests study participants have to stay at the university and are not allowed to eat These test days will take place with an interval of three days
Newtricious NWT-03 is a novel dietary egg-protein hydrolysate that has proven benefits on glucose and insulin metabolism as the investigators have recently shown in overweight or obese individuals with T2DM or impaired glucose tolerance Furthermore peripheral vascular function was improved The potential explanation of these effects may arise from the finding that NWT-03 blocks the enzyme dipeptidyl peptidase DPP-IV 7 - a pharmaceutical target for the treatment of T2DM and CVD - that beneficially affects insulin metabolism Compared to the wealth of knowledge about the impact of insulin-sensitivity and peripheral vascular function on the risk of T2DM and CVD emerging evidence also indicates that these risk markers affect cognitive performance This is of great interest since the brain is an insulin sensitive organ and insulin-resistance is associated with cognitive decline while impaired brain vascular function is a key pathophysiological event preceding the development of an impaired cognitive performance A study in mice also showed effects of NWT-03 on neuro-inflammation and oxidative stress in the brain In fact a decreased expression of TNF-α and improved expression of enzymes involved in anti-oxidative processes were observed The investigators have also shown in a similar - but shorter-term 12 weeks - trial beneficial effects of NWT-03 on executive function as the latency of response was reduced manuscripts in preparation In addition the hen egg-white hydrolysate ie LumiVida also improved reaction time in middle-aged women Underlying mechanisms of these hydrolysates on cognitive performance were however not addressed In our review the investigators summarized the impact of dietary factors and exercise on brain vascular function in adults and discussed the relation between these effects with changes in cognitive performance It was concluded that studies on the longer-term effects of lifestyle factors including diet and physical exercise can improve brain vascular function which may contribute to the beneficial effects observed on cognitive performance In addition longer-term effects remain unknown and only a limited number of parameters related to cognitive performance were studied Therefore the investigators propose to perform a long-term placebo-controlled double blind intervention study including functional outcome parameters and study in vivo effects of NWT-03 on brain vascular function which is a potential target to prevent or slow-down cognitive impairments and improve cognitive performance Focus will be on older adults aged 60-75 years with a Body Mass Index BMI between 25-35 kgm2 overweight or obese and subjective cognitive decline SCD as assessed with the cognitive failure questionnaire These individuals are known to be at increased risk of cognitive impairment allowing for improvement by the intervention
Secondary study endpoints are effects on insulin-sensitivity and peripheral vascular function which are risk markers that may affect cognitive performance Finally the investigators will focus on other potential mechanisms underlying effects on brain function ie ambulatory blood pressure structural brain status humoral factors and the more conventional cardiometabolic risk markers and other perceivable benefits including general well-being quality of life sleep characteristics and mood and physical fitness
Effects will be investigated using innovative and emerging non-invasive brain magnetic resonance imaging MRI-perfusion methods while focusing on whole brain and cognitive-control brain areas plus cognitive performance tests Furthermore the investigators have reviewed that cerebral blood flow in gray matter is a sensitive and straightforward marker of brain vascular function which correlates with cognitive performance Of note lower cerebral blood flow is associated with accelerated cognitive decline and increased risk of dementia in the general population based on results of the Rotterdam prospective cohort study Cerebral blood flow changes will be quantified on a Siemens 3 Tesla Magnetom Prisma Fit scanner at the Scannexus research facilities by the non-invasive gold standard approach the MRI perfusion method pseudo-continuous Arterial Spin LabelingCognitive performance will be assessed using CANTAB ie Cambridge Neuropsychological Test Automated Battery These validated assessments for state-of-the-art cognitive testing focus on the main cognitive domains ie executive function attention and memory Brain vascular function will be investigated using innovative and emerging non-invasive brain magnetic resonance imaging MRI-perfusion methods while focusing on whole brain and cognitive-control brain areas plus cognitive performance tests Furthermore the investigators have reviewed that cerebral blood flow in gray matter is a sensitive and straightforward marker of brain vascular function which correlates with cognitive performance Of note lower cerebral blood flow is associated with accelerated cognitive decline and increased risk of dementia in the general population based on results of the Rotterdam prospective cohort study Cerebral blood flow changes will be quantified on a Siemens 3 Tesla Magnetom Prisma Fit scanner at the Scannexus research facilities by the non-invasive gold standard approach the MRI perfusion method pseudo-continuous Arterial Spin Labeling
Considering the background information given in the previous paragraph the following research questions are formulated
Primary research question
What are the effects in older adults with a BMI between 25-35 kgm2 and SCD of a 36-weeks NWT-03 intervention on i cognitive performance using a neurophysiological test battery and ii cerebral blood flow as quantified by the MRI-perfusion method Arterial Spin Labelling
Major null hypotheses H0
1 A 36-weeks NWT-03 intervention does not significantly affect cognitive performance in older adults with a BMI between 25-35 kgm2 and SCD
2 A 36-weeks NWT-03 intervention does not significantly affect cerebral blood flow as assessed by Arterial Spin Labelling in older adults with a BMI between 25-35 kgm2 and SCD
Major alternate hypotheses Ha
1 A 36-weeks NWT-03 intervention significantly affects cognitive performance in older adults with a BMI between 25-35 kgm2 and SCD
2 A 36-weeks NWT-03 intervention significantly affects cerebral blood flow as assessed by Arterial Spin Labelling in older adults with a BMI between 25-35 kgm2 and SCD
Secondary research question
What are the effects in older adults with SCD of a 36-weeks NWT-03 intervention on insulin sensitivity and peripheral vascular function which are risk markers for T2DM and CVD
Exploratory research questions
What are the effects in older adults with subjective cognitive decline SCD of a 36-weeks NWT-03 intervention on
mechanisms underlying effects on brain function including structural brain status humoral factors and the more conventional cardiometabolic risk markers
perceivable consumer benefits including physical fitness and general well-being
A randomized placebo-controlled trial with a parallel design will be conducted
Before screening subjects will be informed about the procedures and informed consent will be obtained Following screening study participants that fulfill all inclusion criteria and are willing to participate will be asked to participate in this study
Subjects will be informed about their screening results including anthropometric measures weight length body mass index systolic and diastolic blood pressure SBP and DBP serum total cholesterol and triacylglycerol concentrations and plasma glucose concentrations When treatment with drugs or lifestyle interventions is indicated according to the Standards of the Dutch general practitioners community NHG subjects will be advised to consult their general practitioner Study results obtained during the intervention trial ie brain vascular function will be reported in a descriptive way at a group level for example brain vascular function is improved because no accepted normal ranges exist for these measurements
On the days before blood sampling adults are asked not to perform any strenuous physical exercise or to consume alcoholic beverages On the morning of blood sampling - after a 12-hour overnight fast from 800 PM - study subjects are only allowed to drink a glass of water Subjects are also asked not to change their habitual diet during the study Finally subjects are asked to come to the Metabolic Research Unit MRUM by public transport or car and not by foot or bike to standardize research measurements as much as possible
At baseline and after 18 weeks anthropometric measurements will be performed and a fasting blood sample will be drawn At baseline and after 36 weeks subjects have to attend two times the research facilities to perform the follow-up measurements once for the Day A measurements and once for the Day B measurements During these tests study participants have to stay at the university and are not allowed to eat These test days will take place with an interval of three days
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None