Dietary ProteinmTORNCT03946774
Dietary Protein and Monocyte/Macrophage Mammalian Target of Rapamycin (mTOR) Signaling
A study testing Dietary protein shake in people with Dietary Protein, run by Washington University School of Medicine at 1 site in United States.
Trial summary
High protein low carbohydrate diets have become popular in recent years to help facilitate weight loss. It is controversial if these diets are associated with an increased risk of cardiovascular disease. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Dietary Protein
- What is being tested?
- Dietary protein shake
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2019to 4 May 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18+ years of age
- Able to drink milk based protein shake
Who cannot join
- Current Pregnancy
- Any food allergies
- Personal Hx of Diabetes
- Personal Hx of Heart Disease
- Personal Hx of High blood pressure
- Personal Hx of Stroke
Show all 12Show fewer
- Personal Hx of Cancer
- Personal Hx of Organ transplant
- Taking Rapamycin/Sirolimus
- Taking Torisel/Temsirolimus
- Taking Afinitor/Everolimus
- Taking any statin medication (eg.simvastatin/atorvastatin/rosuvastatin etc)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Acute Effects of Dietary Protein on Monocyte/Macrophage mTOR Signaling and Downstream Sequela
High protein low carbohydrate diets have become popular in recent years to help facilitate weight loss. It is controversial if these diets are associated with an increased risk of cardiovascular disease.
The investigators propose to administer high and low protein shakes to participants and measure effects on circulating monocytes, immune cells critical to the development of atherosclerosis and cardiovascular disease. In order to study circulating monocytes, blood will be collected from the study participants just prior to drinking the shake, and then 1 and 4 hours after drinking the shake.
In order to assess functional effects on monocytes, investigators will perform a series of assays comparing the results between individuals who drank high protein vs low protein shakes.
Read the detailed description
Cardiovascular disease remains the leading cause of death globally with obesity as of one of the dominant modifiable risk factors. Obesity is also a precursor to several other cardiovascular risk factors including hypertension, hyperlipidemia, and diabetes. Almost all weight loss efforts utilize dietary modification with high protein/low carbohydrate diets serving as one of the most popular approaches. Despite the metabolic benefits of high dietary protein, recent studies have raised a concerning association with increased risk of atherosclerosis and cardiovascular disease. Although this remains controversial, there is some animal data showing evidence of dietary protein's proatherogenic role. These data are correlative and no mechanistic studies have been undertaken.
The downstream events after protein ingestion involve digestion of the protein into amino acids, increases in blood amino acids, and distribution to target tissues. Mouse models have definitively shown that circulating monocytes and macrophages of arterial blood vessels are particularly sensitive to this amino acid load with robust activation of the mTOR (mammalian target of rapamycin) signaling pathway. This in turn leads to inhibition of essential degradative processes of the macrophage such as autophagy and promotes release of pro-inflammatory cytokines. Thus, macrophage function in vascular beds becomes pathogenic leading to atherogenesis and cardiovascular disease
The translation of these mechanistic studies in animal models to human is the next obvious step in this research. However, no studies have elucidated the mechanisms of monocyte activation and function following administration of high dietary protein in humans. The investigators propose a pilot study to bridge an important gap in translational research which will elucidate the mechanisms by which dietary protein affects human monocyte function and the risk of atherosclerotic plaque formation. Specifically, the investigators will evaluate the acute activation of mTOR signaling and downstream sequelae in circulating monocytes following the administration of protein shakes. This study will address the hypothesis that humans exposed to high dietary protein will have significantly higher post-prandial monocyte mTOR activation with concomitant development of impaired degradative capacity and a proinflammatory state.
An understanding of these mechanisms has broad implications in the evaluation and future therapeutic interventions of cardiovascular disease.
In addition, this can provide a valuable clinical tool for health care providers in educating patients on dietary changes to ameliorate cardiovascular risk.
- Conditions
- Dietary Protein
- Being tested
- Dietary protein shake
- Keywords
- Atherosclerosis, Macrophage/monocyte, mTOR, Autophagy, Apoptosis, Inflammation
- Medical subject headings
- Atherosclerosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary protein shakeDietary supplement
It is a milk based protein shake. Ingredients include a combination of the following depending on protein content: Boost Plus (a commercial supplement), Unjury (a commercial whey protein isolate), nonfat dry milk powder, Sol Carb (commercial supplement composed of a carbohydrate polymer), canola oil, and water.
In order to ensure consistency across all participants each beverage will be prepared in the Clinical Translational Research Unit Metabolic Kitchen under the supervision of a registered dietitian prior to the study participant's visit. Ingredients are individually weighed on a food scale by metabolic kitchen staff to the nearest 0.1 g and then mixed using a magnetic stir plate.
Nutritional breakdown of the smoothies (high versus low protein):
High protein drink nutrition: 500 kcal per serving, 50% protein, 17% fat, and 36% carbohydrate.
Low (standard) protein drink nutrition: 500 kcal per serving, 10% protein, 17% fat, and 73% carbohydrate.
| Study group | Role | What they receive |
|---|---|---|
| High protein | Active comparator | Subjects getting high protein shake Receives: Dietary Supplement: Dietary protein shake |
| Low protein | Active comparator | Subjects getting low protein shake Receives: Dietary Supplement: Dietary protein shake |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of amino acid levels and mTOR activation in circulating monocytes isolated from subjects ingesting high vs low protein drinks.
Changes in amino acid levels and corresponding changes in mTOR activation will be quantified at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 3 hours after ingestion of a protein shake.
Measured: 0 Hour, 1 Hour, and 3 Hours
Secondary outcomes (3)
Determination of changes in autophagy and apoptosis markers in circulating monocytes over time after ingestion of a protein shake
Blood collected at three different time points (0, 1 and 3 hours) will be used to measure changes in markers of autophagy and apoptosis at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 3 hours after ingestion of a protein shake.
Measured: 0 Hour, 1 Hour and 3 Hours
Determination of changes in reactive oxygen species in circulating monocytes over time after ingestion of a protein shake.
Blood collected at three different time points (0, 1 and 3 hours) will be used to measure changes in levels of reactive oxygen species at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 3 hours after ingestion of a protein shake.
Measured: 0 Hour, 1 Hour, and 3 Hours
Determination of changes in inflammatory markers in circulating monocytes over time after ingestion of a protein shake.
Blood collected at three different time points (0, 1 and 3 hours) will be used to measure changes in cytokines at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 3 hours after ingestion of a protein shake.
Measured: 0 Hour, 1 Hour, and 3 Hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2019
- Study start1 Oct 2019
- Primary completion4 May 2023
- Study completion4 May 2023
Why it stopped: Temporarily paused due to COVID-19 and expected to resume. This is not a suspension of IRB approval. PI has left the institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dietary ProteinStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03946774
- Sponsor's protocol ID
- 201808084
- Acronym
- mTOR
- Status last verified
- Oct 2024
- First submitted
- 12 Mar 2019
- Last updated
- 26 Oct 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Effects of Dietary Protein on Monocyte/Macrophage mTOR Signaling and Downstream Sequela
- ClinicalTrials.gov ID
- NCT03946774
- Acronym / sponsor ID
- mTOR / 201808084
- Conditions
- Dietary Protein
- Keywords
- Atherosclerosis, Macrophage/monocyte, mTOR, Autophagy, Apoptosis, Inflammation
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Temporarily paused due to COVID-19 and expected to resume. This is not a suspension of IRB approval. PI has left the institution.
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 4 May 2023 (actual)
- Study completion
- 4 May 2023 (actual)
- First posted
- 13 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
High protein low carbohydrate diets have become popular in recent years to help facilitate weight loss. It is controversial if these diets are associated with an increased risk of cardiovascular disease.
The investigators propose to administer high and low protein shakes to participants and measure effects on circulating monocytes, immune cells critical to the development of atherosclerosis and cardiovascular disease. In order to study circulating monocytes, blood will be collected from the study participants just prior to drinking the shake, and then 1 and 4 hours after drinking the shake.
In order to assess functional effects on monocytes, investigators will perform a series of assays comparing the results between individuals who drank high protein vs low protein shakes.
Detailed description
Cardiovascular disease remains the leading cause of death globally with obesity as of one of the dominant modifiable risk factors. Obesity is also a precursor to several other cardiovascular risk factors including hypertension, hyperlipidemia, and diabetes. Almost all weight loss efforts utilize dietary modification with high protein/low carbohydrate diets serving as one of the most popular approaches. Despite the metabolic benefits of high dietary protein, recent studies have raised a concerning association with increased risk of atherosclerosis and cardiovascular disease. Although this remains controversial, there is some animal data showing evidence of dietary protein's proatherogenic role. These data are correlative and no mechanistic studies have been undertaken.
The downstream events after protein ingestion involve digestion of the protein into amino acids, increases in blood amino acids, and distribution to target tissues. Mouse models have definitively shown that circulating monocytes and macrophages of arterial blood vessels are particularly sensitive to this amino acid load with robust activation of the mTOR (mammalian target of rapamycin) signaling pathway. This in turn leads to inhibition of essential degradative processes of the macrophage such as autophagy and promotes release of pro-inflammatory cytokines. Thus, macrophage function in vascular beds becomes pathogenic leading to atherogenesis and cardiovascular disease
The translation of these mechanistic studies in animal models to human is the next obvious step in this research. However, no studies have elucidated the mechanisms of monocyte activation and function following administration of high dietary protein in humans. The investigators propose a pilot study to bridge an important gap in translational research which will elucidate the mechanisms by which dietary protein affects human monocyte function and the risk of atherosclerotic plaque formation. Specifically, the investigators will evaluate the acute activation of mTOR signaling and downstream sequelae in circulating monocytes following the administration of protein shakes. This study will address the hypothesis that humans exposed to high dietary protein will have significantly higher post-prandial monocyte mTOR activation with concomitant development of impaired degradative capacity and a proinflammatory state.
An understanding of these mechanisms has broad implications in the evaluation and future therapeutic interventions of cardiovascular disease.
In addition, this can provide a valuable clinical tool for health care providers in educating patients on dietary changes to ameliorate cardiovascular risk.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High protein | Active comparator | Dietary Supplement: Dietary protein shakeSubjects getting high protein shake |
| Low protein | Active comparator | Dietary Supplement: Dietary protein shakeSubjects getting low protein shake |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 18+ years of age
- Able to drink milk based protein shake
Key exclusion criteria (12 listed)
- Current Pregnancy
- Any food allergies
- Personal Hx of Diabetes
- Personal Hx of Heart Disease
- Personal Hx of High blood pressure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dietary protein shakeIt is a milk based protein shake. Ingredients include a combination of the following depending on protein content: Boost Plus (a commercial supplement), Unjury (a commercial whey protein isolate), nonfat dry milk powder, Sol Carb (commercial supplement composed of a carbohydrate polymer), canola oil, and water. In order to ensure consistency across all participants each beverage will be prepared in the Clinical Translational Research Unit Metabolic Kitchen under the supervision of a registered dietitian prior to the study participant's visit. Ingredients are individually weighed on a food scale by metabolic kitchen staff to the nearest 0.1 g and then mixed using a magnetic stir plate. Nutritional breakdown of the smoothies (high versus low protein): High protein drink nutrition: 500 kcal per serving, 50% protein, 17% fat, and 36% carbohydrate. Low (standard) protein drink nutrition: 500 kcal per serving, 10% protein, 17% fat, and 73% carbohydrate. | Dietary supplement | High protein, Low protein |
Primary outcome
Determination of amino acid levels and mTOR activation in circulating monocytes isolated from subjects ingesting high vs low protein drinks.
Time frame: 0 Hour, 1 Hour, and 3 Hours
Changes in amino acid levels and corresponding changes in mTOR activation will be quantified at baseline (time 0 hour prior to ingestion of a protein shake), then at 1 and 3 hours after ingestion of a protein shake.
3 secondary outcomes
Determination of changes in autophagy and apoptosis markers in circulating monocytes over time after ingestion of a protein shake
Time frame: 0 Hour, 1 Hour and 3 Hours
Determination of changes in reactive oxygen species in circulating monocytes over time after ingestion of a protein shake.
Time frame: 0 Hour, 1 Hour, and 3 Hours
Determination of changes in inflammatory markers in circulating monocytes over time after ingestion of a protein shake.
Time frame: 0 Hour, 1 Hour, and 3 Hours
Results and safety
The study was stopped early (reason given: Temporarily paused due to COVID-19 and expected to resume. This is not a suspension of IRB approval. PI has left the institution.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dietary protein shake in people with Dietary Protein, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Temporarily paused due to COVID-19 and expected to resume. This is not a suspension of IRB approval. PI has left the institution.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of amino acid levels and mTOR activation in circulating monocytes isolated from subjects ingesting high vs low protein drinks. (time frame: 0 Hour, 1 Hour, and 3 Hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2024.