AtherosclerosisNCT03173677
Macrophage Polarization in Response to Macronutrient Intake in Healthy Humans: A Randomized Clinical Study
A study testing Lipid Intake, Glucose intake and Protein intake in people with Atherosclerosis, run by King Saud Bin Abdulaziz University for Health Sciences.
Trial summary
Macrophages can exhibit distinct phenotypes and functions in response to stimuli and can polarize into one of three distinct phenotypes: a pro-inflammatory (M1), an anti-inflammatory pro-tissue (M2) and metabolically-activated (MMe) macrophage phenotypes. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Atherosclerosis
- What is being tested?
- Lipid Intake, Glucose intake and Protein intake
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- No sites listed yet
- Study dates
- 2 Feb 2016to 29 Apr 2016
- 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
- Normal weight (BMI 18.5-25)
- Healthy adults evident by: physical examination, normal lipid profile, normal renal and liver function tests.
Who cannot join
- Renal disease
- Hepatic disease
- Cardiovascular disease
- Using multivitamins
- Using NSAIDS
About this study
Official title: Monocyte Differentiation and Macrophage Polarization in Circulation in Response to Macronutrient Intake in Healthy Humans: A Randomized Clinical Study
Macrophages can exhibit distinct phenotypes and functions in response to stimuli and can polarize into one of three distinct phenotypes: a pro-inflammatory (M1), an anti-inflammatory pro-tissue (M2) and metabolically-activated (MMe) macrophage phenotypes. Thirty-six healthy volunteers were recruited and randomized into one of three macronutrient intake groups (glucose, lipids, proteins). This study measured the effects of macronutrient intake on the macrophage differentiation.
Read the detailed description
Thirty-six normal healthy adult volunteers of normal weight were recruited into the study. All were normotensive, had a normal lipid profile, normal renal and liver function tests, and were not on any medications. All subjects gave their written, informed consent. Institutional Review Board (IRB) of the Ministry of National Guard Health Affairs (MNGHA) approved the study protocol. The 36 participants were randomly assigned by the primary investigator (PI) following simple randomization procedure (computerized random numbers) to three different groups, each received one type of macronutrient (Glucose, whey proteins or lipids). Following an overnight fast, a baseline blood sample was taken. Subjects were then given either 300 calories of glucose (NERL Trutol 75) or lipids (90 grams whipping cream, 31.5 grams fat, 1.7 grams protein and 2.25 grams carbohydrate) or protein (Isopure unflavored Whey proteins isolate (WPI) powder containing 26 grams per serving of 100% WPI, stripped of fat, carbs, fillers, sugars and lactose) solution over 5 minutes. Cream and protein preparations were diluted with water up to 300 mL solutions. Further blood samples were obtained at 1, 2 and 3 hours after the macronutrient intake. Subjects, either one week before or after the macronutrient challenge, were given 300 mL of water to drink in the fasting state. Blood samples were obtained before and at 1, 2 and 3 h after water intake as well. Each subject served as his/her own control and was randomly given macronutrient or water intake.
- Conditions
- Atherosclerosis
- Being tested
- Lipid Intake, Glucose intake, Protein intake
- Keywords
- Mononuclear cells, Whey proteins, Metabolically-Activated Macrophage, Macrophage Polarization, Macronutrients
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lipid IntakeDietary supplement
90 grams whipping cream, 31.5 grams fat, 1.7 grams protein, and 2.25 grams carbohydrate
Glucose intakeDietary supplement
300 calories of glucose
Protein intakeDietary supplement
Isopure unflavored Whey proteins isolate (WPI) powder containing 26 grams per serving of 100% WPI, stripped of fat, carbs, fillers, sugars, and lactose
| Study group | Role | What they receive |
|---|---|---|
| Lipid intake | Active comparator | 12 subjects had 300 Calories of lipids or 300 mL of water. Blood samples were drawn at 0, 1, 2, and 3 hrs post intake. There was a one week period between the 2 intakes. Receives: Dietary Supplement: Lipid Intake |
| Glucose intake | Active comparator | 12 subjects had 300 Calories of glucose or 300 mL of water. Blood samples were drawn at 0, 1, 2, and 3 hrs post intake. There was a one week period between the 2 intakes. Receives: Dietary Supplement: Glucose intake |
| Protein intake | Active comparator | 12 subjects had 300 Calories Whey protein intake or 300 mL of water. Blood samples were drawn at 0, 1, 2, and 3 hrs post intake. There was a one week period between the 2 intakes. Receives: Dietary Supplement: Protein intake |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection of markers of M1 and M2 macrophages
The following markers were used to detect M1 and M2 macrophages (M1:CD86, IL-6, CD11c, and CD169, and M2: CD206, CD163, and CD36)
Measured: Subject recruitment, enrollment and sample collection were carried out in a period of 3 months. Baseline blood samples were drawn before the caloric or water intake, and subsequent blood samples were drawn at 1-, 2- and 3-hour intervals post the intake
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2017
- Study start2 Feb 2016
- Primary completion24 Apr 2016
- Study completion29 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- King Saud Bin Abdulaziz University for Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmad Aljada, King Saud Bin Abdulaziz University for Health Sciences
- Investigators
- Awad Alshahrani, MD, Principal investigator, Ministry of Natioanl Guard Health Affairs
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03173677
- Sponsor's protocol ID
- SP15/026
- Status last verified
- May 2017
- First submitted
- 28 May 2017
- Last updated
- 2 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Italiani P, Boraschi D. From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation. Front Immunol. 2014 Oct 17;5:514. doi: 10.3389/fimmu.2014.00514. eCollection 2014.
PubMed 25368618Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 2014 Mar 3;6:13. doi: 10.12703/P6-13. eCollection 2014.
PubMed 24669294Billiau A, Matthys P. Interferon-gamma: a historical perspective. Cytokine Growth Factor Rev. 2009 Apr;20(2):97-113. doi: 10.1016/j.cytogfr.2009.02.004. Epub 2009 Mar 5.
PubMed 19268625Guha M, Mackman N. LPS induction of gene expression in human monocytes. Cell Signal. 2001 Feb;13(2):85-94. doi: 10.1016/s0898-6568(00)00149-2.
PubMed 11257452Feghali CA, Wright TM. Cytokines in acute and chronic inflammation. Front Biosci. 1997 Jan 1;2:d12-26. doi: 10.2741/a171.
PubMed 9159205Stein M, Keshav S, Harris N, Gordon S. Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med. 1992 Jul 1;176(1):287-92. doi: 10.1084/jem.176.1.287.
PubMed 1613462Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993 Jan 1;259(5091):87-91. doi: 10.1126/science.7678183.
PubMed 7678183Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999 Dec 8;282(22):2131-5. doi: 10.1001/jama.282.22.2131.
PubMed 10591334Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998 Mar;83(3):847-50. doi: 10.1210/jcem.83.3.4660.
PubMed 9506738Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006 Jul;116(7):1793-801. doi: 10.1172/JCI29069.
PubMed 16823477Stoger JL, Gijbels MJ, van der Velden S, Manca M, van der Loos CM, Biessen EA, Daemen MJ, Lutgens E, de Winther MP. Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis. 2012 Dec;225(2):461-8. doi: 10.1016/j.atherosclerosis.2012.09.013. Epub 2012 Sep 26.
PubMed 23078881Mohanty P, Ghanim H, Hamouda W, Aljada A, Garg R, Dandona P. Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells. Am J Clin Nutr. 2002 Apr;75(4):767-72. doi: 10.1093/ajcn/75.4.767.
PubMed 11916766
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monocyte Differentiation and Macrophage Polarization in Circulation in Response to Macronutrient Intake in Healthy Humans: A Randomized Clinical Study
- ClinicalTrials.gov ID
- NCT03173677
- Acronym / sponsor ID
- SP15/026
- Conditions
- Atherosclerosis
- Keywords
- Mononuclear cells, Whey proteins, Metabolically-Activated Macrophage, Macrophage Polarization, Macronutrients
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- King Saud Bin Abdulaziz University for Health SciencesUniversity, hospital or other
- Study start
- 2 Feb 2016 (actual)
- Primary completion
- 24 Apr 2016 (actual)
- Study completion
- 29 Apr 2016 (actual)
- First posted
- 2 Jun 2017 (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.
Macrophages can exhibit distinct phenotypes and functions in response to stimuli and can polarize into one of three distinct phenotypes: a pro-inflammatory (M1), an anti-inflammatory pro-tissue (M2) and metabolically-activated (MMe) macrophage phenotypes. Thirty-six healthy volunteers were recruited and randomized into one of three macronutrient intake groups (glucose, lipids, proteins). This study measured the effects of macronutrient intake on the macrophage differentiation.
Detailed description
Thirty-six normal healthy adult volunteers of normal weight were recruited into the study. All were normotensive, had a normal lipid profile, normal renal and liver function tests, and were not on any medications. All subjects gave their written, informed consent. Institutional Review Board (IRB) of the Ministry of National Guard Health Affairs (MNGHA) approved the study protocol. The 36 participants were randomly assigned by the primary investigator (PI) following simple randomization procedure (computerized random numbers) to three different groups, each received one type of macronutrient (Glucose, whey proteins or lipids). Following an overnight fast, a baseline blood sample was taken. Subjects were then given either 300 calories of glucose (NERL Trutol 75) or lipids (90 grams whipping cream, 31.5 grams fat, 1.7 grams protein and 2.25 grams carbohydrate) or protein (Isopure unflavored Whey proteins isolate (WPI) powder containing 26 grams per serving of 100% WPI, stripped of fat, carbs, fillers, sugars and lactose) solution over 5 minutes. Cream and protein preparations were diluted with water up to 300 mL solutions. Further blood samples were obtained at 1, 2 and 3 hours after the macronutrient intake. Subjects, either one week before or after the macronutrient challenge, were given 300 mL of water to drink in the fasting state. Blood samples were obtained before and at 1, 2 and 3 h after water intake as well. Each subject served as his/her own control and was randomly given macronutrient or water intake.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lipid intake | Active comparator | Dietary Supplement: Lipid Intake12 subjects had 300 Calories of lipids or 300 mL of water. Blood samples were drawn at 0, 1, 2, and 3 hrs post intake. There was a one week period between the 2 intakes. |
| Glucose intake | Active comparator | Dietary Supplement: Glucose intake12 subjects had 300 Calories of glucose or 300 mL of water. Blood samples were drawn at 0, 1, 2, and 3 hrs post intake. There was a one week period between the 2 intakes. |
| Protein intake | Active comparator | Dietary Supplement: Protein intake12 subjects had 300 Calories Whey protein intake or 300 mL of water. Blood samples were drawn at 0, 1, 2, and 3 hrs post intake. There was a one week period between the 2 intakes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Normal weight (BMI 18.5-25)
- Healthy adults evident by: physical examination, normal lipid profile, normal renal and liver function tests.
Key exclusion criteria (5 listed)
- Renal disease
- Hepatic disease
- Cardiovascular disease
- Using multivitamins
- Using NSAIDS
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 |
|---|---|---|
| Lipid Intake90 grams whipping cream, 31.5 grams fat, 1.7 grams protein, and 2.25 grams carbohydrate | Dietary supplement | Lipid intake |
| Glucose intake300 calories of glucose | Dietary supplement | Glucose intake |
| Protein intakeIsopure unflavored Whey proteins isolate (WPI) powder containing 26 grams per serving of 100% WPI, stripped of fat, carbs, fillers, sugars, and lactose | Dietary supplement | Protein intake |
Primary outcome
Detection of markers of M1 and M2 macrophages
Time frame: Subject recruitment, enrollment and sample collection were carried out in a period of 3 months. Baseline blood samples were drawn before the caloric or water intake, and subsequent blood samples were drawn at 1-, 2- and 3-hour intervals post the intake
The following markers were used to detect M1 and M2 macrophages (M1:CD86, IL-6, CD11c, and CD169, and M2: CD206, CD163, and CD36)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2017.
- Background: PubMed 25368618Italiani P, Boraschi D. From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation. Front Immunol. 2014 Oct 17;5:514. doi: 10.3389/fimmu.2014.00514. eCollection 2014.
- Background: PubMed 24669294Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 2014 Mar 3;6:13. doi: 10.12703/P6-13. eCollection 2014.
- Background: PubMed 19268625Billiau A, Matthys P. Interferon-gamma: a historical perspective. Cytokine Growth Factor Rev. 2009 Apr;20(2):97-113. doi: 10.1016/j.cytogfr.2009.02.004. Epub 2009 Mar 5.
- Background: PubMed 11257452Guha M, Mackman N. LPS induction of gene expression in human monocytes. Cell Signal. 2001 Feb;13(2):85-94. doi: 10.1016/s0898-6568(00)00149-2.
- Background: PubMed 9159205Feghali CA, Wright TM. Cytokines in acute and chronic inflammation. Front Biosci. 1997 Jan 1;2:d12-26. doi: 10.2741/a171.
- Background: PubMed 1613462Stein M, Keshav S, Harris N, Gordon S. Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med. 1992 Jul 1;176(1):287-92. doi: 10.1084/jem.176.1.287.
- Background: PubMed 7678183Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993 Jan 1;259(5091):87-91. doi: 10.1126/science.7678183.
- Background: PubMed 10591334Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999 Dec 8;282(22):2131-5. doi: 10.1001/jama.282.22.2131.
- Background: PubMed 9506738Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998 Mar;83(3):847-50. doi: 10.1210/jcem.83.3.4660.
- Background: PubMed 16823477Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006 Jul;116(7):1793-801. doi: 10.1172/JCI29069.
- Background: PubMed 23078881Stoger JL, Gijbels MJ, van der Velden S, Manca M, van der Loos CM, Biessen EA, Daemen MJ, Lutgens E, de Winther MP. Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis. 2012 Dec;225(2):461-8. doi: 10.1016/j.atherosclerosis.2012.09.013. Epub 2012 Sep 26.
- Background: PubMed 11916766Mohanty P, Ghanim H, Hamouda W, Aljada A, Garg R, Dandona P. Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells. Am J Clin Nutr. 2002 Apr;75(4):767-72. doi: 10.1093/ajcn/75.4.767.
- 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.
Awad Alshahrani, MD principal investigator
Ministry of Natioanl Guard Health Affairs
Questions about this trial
What is this clinical trial studying?
A study testing Lipid Intake, Glucose intake and Protein intake in people with Atherosclerosis, run by King Saud Bin Abdulaziz University for Health Sciences.
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 5 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: finished, as of the sponsor's last update on 2 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Detection of markers of M1 and M2 macrophages (time frame: Subject recruitment, enrollment and sample collection were carried out in a period of 3 months. Baseline blood samples were drawn before the caloric or water intake, and subsequent blood samples were drawn at 1-, 2- and 3-hour intervals post the intake). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03173677, which also lists 12 linked publications.
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 2 Jun 2017.