HealthyNCT05906641
Modulation of Secondary Bile Acids Through the Intestinal Microbiota After Consumption of a High-protein Diet.
A study testing High-protein diet in people with Healthy, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site in Mexico.
Trial summary
This study will investigate whether changes in the gut microbiota generated after the consumption of a high protein diet in healthy subjects, modify the production of secondary bile acids. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- High-protein diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteMexico
- Study dates
- 1 Aug 2023to 30 Dec 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
- Male and female.
- Between 18 and older
- BMI ≥ 18.5 and ≤ 24.9 kg/m2.
- Healthy
- Willing and able to sign written informed consent prior to trial entry
Who cannot join
- Have previously diagnosed with any chronic disease
- Patients with high blood pressure.
- Patients who have suffered a cardiovascular event.
- Patients with gastrointestinal diseases.
- Weight loss > 3 kg in the last 3 months.
- Catabolic diseases such as cancer and acquired immunodeficiency syndrome.
Show all 19Show fewer
- Pregnancy status.
- Antibiotic consumption 3 months prior to the study.
- Be an undergraduate or graduate student within the Institute.
- Subjects with creatinine > 1.3 mg/dL for men and >1 mg/dL for women and ureic nitrogen > 20 mg/dL.
- Positive smoking.
- Drug treatment:
- Antihypertensive drugs or treatment
- Treatment with hypoglycemic agents or insulin and antidiabetic drugs.
- Treatment with statins, fibrates or other drugs to control dyslipidemia.
- Use of antibiotics in the three months prior to the study.
- Use of steroid drugs, chemotherapy, immunosuppressants, or radiation therapy.
- Anorexigenic or that accelerate weight loss such as sibutramine or orlistat.
- Probiotic, prebiotic or symbiotic supplements.
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran
Mexico City
About this study
This study will investigate whether changes in the gut microbiota generated after the consumption of a high protein diet in healthy subjects, modify the production of secondary bile acids. In addition, it will be seen whether a high protein intake modifies postprandial glucose response and its relationship with gut microbiota composition.
Read the detailed description
The gut microbiota is a set of microorganisms that inhabit the human digestive tract and are fundamental for the health of the host. Among the functions of the gut microbiota is the production of metabolites, such as the production of secondary bile acids from primary bile acids. On the other hand, evidence has shown that the amount of protein intake can modify the composition of the gut microbiota and in turn it increase the concentration of secondary biles acids in animal models. In addition, the consumption of a high-protein diet has been related to a decrease in postprandial glucose concentrations. Therefore, the aim of this study is to evaluate changes in secondary bile acids concentration derived from gut microbiota after the consumption of a high-protein diet in healthy subjects. Subjects with a BMI between 18.5 and 24.9 kg/m2 will be selected and will be continuously monitored with a continuous glucose monitor through 15 days. During the first 7 days participants will follow an isocaloric diet (50% carbohydrates, 30% fat and 20% protein), while during the last 7 days participants will receive an intervention with a supplement of protein (calcium caseinate) which will increase their protein intake to 30% of the total energy requirement. At the initial and final visit, blood samples will be taken for determination of biochemical parameters, amino acids and primary bile acids and a stool sample will be requested for sequencing gut microbiota and determined secondary bile acids.
- Conditions
- Healthy
- Being tested
- High-protein diet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-protein dietDietary supplement
Protein intake will be increased to be 30% calories from protein with calcium caseinate.
| Study group | Role | What they receive |
|---|---|---|
| High-protein diet | Experimental | Participants will receive an isocaloric diet with a distribution of 50% carbohydrates, 30% fat and 20% protein for the two-week intervention. Additionally, they will receive a dietary supplement for the second week that will contribute another 10% of protein, obtaining 30% of protein consumption in the second week. Receives: Dietary Supplement: High-protein diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in faecal microbiota composition in response to high-protein diet
Changes to the faecal microbiota will be assessed on a high-protein diet compared to an isocaloric diet in a short period of time. Bacterial composition was measured by 16 ribosomal sequencing at baseline at day 7 and at the end of the second week. The relative change of each bacterial taxon was calculated based on the abundance of the given bacteria at baseline, at 7 days and after 14 days
Measured: baseline, 7 days and 14 days
Increase of secondary bile acids production
Increase in the concentrations of lithocholic acid and deoxycholic acid in feces (mg/g of feces) measured by the method gas chromatography represented with the units micromol.
Measured: baseline, 7 days and 14 days
Secondary outcomes (3)
Regulation of postprandial glucose response
Change in interstitial glucose determined by a continuous glucose monitor (mg/dL) within two weeks.
Measured: 14 days
Increase in serum glucagon concentration
Change in serum glucagon concentration determined by ELISA (pg/mL)
Measured: Baseline, 7 days and 14 days
Decrease in serum insulin concentration
Change in serum insulin concentration determined by ELISA (pg/mL)
Measured: Baseline, 7 days and 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2023
- Study start1 Aug 2023
- Primary completion30 Nov 2023
- Study completion30 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Armando Tovar, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
- Investigators
- Maria del Rocio Guizar-Heredia, Master, Study chair, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiranArmando R Tovar, Doctor, Principal investigator, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiranMartha Guevara-Cruz, Doctor, Study director, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05906641
- Sponsor's protocol ID
- 4532
- Status last verified
- Mar 2024
- First submitted
- 7 Jun 2023
- Last updated
- 5 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
de Aguiar Vallim TQ, Tarling EJ, Edwards PA. Pleiotropic roles of bile acids in metabolism. Cell Metab. 2013 May 7;17(5):657-69. doi: 10.1016/j.cmet.2013.03.013. Epub 2013 Apr 18.
PubMed 23602448Guzior DV, Quinn RA. Review: microbial transformations of human bile acids. Microbiome. 2021 Jun 14;9(1):140. doi: 10.1186/s40168-021-01101-1.
PubMed 34127070Zhao X, Yang X, Hang HC. Chemoproteomic Analysis of Microbiota Metabolite-Protein Targets and Mechanisms. Biochemistry. 2022 Dec 20;61(24):2822-2834. doi: 10.1021/acs.biochem.1c00758. Epub 2022 Jan 6.
PubMed 34989554Pak HH, Cummings NE, Green CL, Brinkman JA, Yu D, Tomasiewicz JL, Yang SE, Boyle C, Konon EN, Ong IM, Lamming DW. The Metabolic Response to a Low Amino Acid Diet is Independent of Diet-Induced Shifts in the Composition of the Gut Microbiome. Sci Rep. 2019 Jan 11;9(1):67. doi: 10.1038/s41598-018-37177-3.
PubMed 30635612Tirosh A, Calay ES, Tuncman G, Claiborn KC, Inouye KE, Eguchi K, Alcala M, Rathaus M, Hollander KS, Ron I, Livne R, Heianza Y, Qi L, Shai I, Garg R, Hotamisligil GS. The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans. Sci Transl Med. 2019 Apr 24;11(489):eaav0120. doi: 10.1126/scitranslmed.aav0120.
PubMed 31019023Kumar DP, Asgharpour A, Mirshahi F, Park SH, Liu S, Imai Y, Nadler JL, Grider JR, Murthy KS, Sanyal AJ. Activation of Transmembrane Bile Acid Receptor TGR5 Modulates Pancreatic Islet alpha Cells to Promote Glucose Homeostasis. J Biol Chem. 2016 Mar 25;291(13):6626-40. doi: 10.1074/jbc.M115.699504. Epub 2016 Jan 12.
PubMed 26757816Murphy EA, Velazquez KT, Herbert KM. Influence of high-fat diet on gut microbiota: a driving force for chronic disease risk. Curr Opin Clin Nutr Metab Care. 2015 Sep;18(5):515-20. doi: 10.1097/MCO.0000000000000209.
PubMed 26154278Singh RK, Chang HW, Yan D, Lee KM, Ucmak D, Wong K, Abrouk M, Farahnik B, Nakamura M, Zhu TH, Bhutani T, Liao W. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017 Apr 8;15(1):73. doi: 10.1186/s12967-017-1175-y.
PubMed 28388917Wei M, Huang F, Zhao L, Zhang Y, Yang W, Wang S, Li M, Han X, Ge K, Qu C, Rajani C, Xie G, Zheng X, Zhao A, Bian Z, Jia W. A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility. EBioMedicine. 2020 May;55:102766. doi: 10.1016/j.ebiom.2020.102766. Epub 2020 May 11.
PubMed 32408110Wu S, Bhat ZF, Gounder RS, Mohamed Ahmed IA, Al-Juhaimi FY, Ding Y, Bekhit AEA. Effect of Dietary Protein and Processing on Gut Microbiota-A Systematic Review. Nutrients. 2022 Jan 20;14(3):453. doi: 10.3390/nu14030453.
PubMed 35276812FOLCH J, LEES M, SLOANE STANLEY GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497-509. No abstract available.
PubMed 13428781Keller S, Jahreis G. Determination of underivatised sterols and bile acid trimethyl silyl ether methyl esters by gas chromatography-mass spectrometry-single ion monitoring in faeces. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Dec 25;813(1-2):199-207. doi: 10.1016/j.jchromb.2004.09.046.
PubMed 15556534Van Elswyk ME, Weatherford CA, McNeill SH. A Systematic Review of Renal Health in Healthy Individuals Associated with Protein Intake above the US Recommended Daily Allowance in Randomized Controlled Trials and Observational Studies. Adv Nutr. 2018 Jul 1;9(4):404-418. doi: 10.1093/advances/nmy026.
PubMed 30032227
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Secondary Bile Acids Through the Intestinal Microbiota After Consumption of a High-protein Diet.
- ClinicalTrials.gov ID
- NCT05906641
- Acronym / sponsor ID
- 4532
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranUniversity, hospital or other
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- 30 Nov 2023 (actual)
- Study completion
- 30 Dec 2023 (actual)
- First posted
- 18 Jun 2023 (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.
This study will investigate whether changes in the gut microbiota generated after the consumption of a high protein diet in healthy subjects, modify the production of secondary bile acids. In addition, it will be seen whether a high protein intake modifies postprandial glucose response and its relationship with gut microbiota composition.
Detailed description
The gut microbiota is a set of microorganisms that inhabit the human digestive tract and are fundamental for the health of the host. Among the functions of the gut microbiota is the production of metabolites, such as the production of secondary bile acids from primary bile acids. On the other hand, evidence has shown that the amount of protein intake can modify the composition of the gut microbiota and in turn it increase the concentration of secondary biles acids in animal models. In addition, the consumption of a high-protein diet has been related to a decrease in postprandial glucose concentrations. Therefore, the aim of this study is to evaluate changes in secondary bile acids concentration derived from gut microbiota after the consumption of a high-protein diet in healthy subjects. Subjects with a BMI between 18.5 and 24.9 kg/m2 will be selected and will be continuously monitored with a continuous glucose monitor through 15 days. During the first 7 days participants will follow an isocaloric diet (50% carbohydrates, 30% fat and 20% protein), while during the last 7 days participants will receive an intervention with a supplement of protein (calcium caseinate) which will increase their protein intake to 30% of the total energy requirement. At the initial and final visit, blood samples will be taken for determination of biochemical parameters, amino acids and primary bile acids and a stool sample will be requested for sequencing gut microbiota and determined secondary bile acids.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High-protein diet | Experimental | Dietary Supplement: High-protein dietParticipants will receive an isocaloric diet with a distribution of 50% carbohydrates, 30% fat and 20% protein for the two-week intervention. Additionally, they will receive a dietary supplement for the second week that will contribute another 10% of protein, obtaining 30% of protein consumption in the second week. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male and female.
- Between 18 and older
- BMI ≥ 18.5 and ≤ 24.9 kg/m2.
- Healthy
- Willing and able to sign written informed consent prior to trial entry
Key exclusion criteria (19 listed)
- Have previously diagnosed with any chronic disease
- Patients with high blood pressure.
- Patients who have suffered a cardiovascular event.
- Patients with gastrointestinal diseases.
- Weight loss > 3 kg in the last 3 months.
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 |
|---|---|---|
| High-protein dietProtein intake will be increased to be 30% calories from protein with calcium caseinate. | Dietary supplement | High-protein diet |
Primary outcome
Changes in faecal microbiota composition in response to high-protein diet
Time frame: baseline, 7 days and 14 days
Changes to the faecal microbiota will be assessed on a high-protein diet compared to an isocaloric diet in a short period of time. Bacterial composition was measured by 16 ribosomal sequencing at baseline at day 7 and at the end of the second week. The relative change of each bacterial taxon was calculated based on the abundance of the given bacteria at baseline, at 7 days and after 14 days
Increase of secondary bile acids production
Time frame: baseline, 7 days and 14 days
Increase in the concentrations of lithocholic acid and deoxycholic acid in feces (mg/g of feces) measured by the method gas chromatography represented with the units micromol.
3 secondary outcomes
Regulation of postprandial glucose response
Time frame: 14 days
Increase in serum glucagon concentration
Time frame: Baseline, 7 days and 14 days
Decrease in serum insulin concentration
Time frame: Baseline, 7 days and 14 days
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 5 Mar 2024.
- Results publication: PubMed 23602448de Aguiar Vallim TQ, Tarling EJ, Edwards PA. Pleiotropic roles of bile acids in metabolism. Cell Metab. 2013 May 7;17(5):657-69. doi: 10.1016/j.cmet.2013.03.013. Epub 2013 Apr 18.
- Results publication: PubMed 34127070Guzior DV, Quinn RA. Review: microbial transformations of human bile acids. Microbiome. 2021 Jun 14;9(1):140. doi: 10.1186/s40168-021-01101-1.
- Results publication: PubMed 34989554Zhao X, Yang X, Hang HC. Chemoproteomic Analysis of Microbiota Metabolite-Protein Targets and Mechanisms. Biochemistry. 2022 Dec 20;61(24):2822-2834. doi: 10.1021/acs.biochem.1c00758. Epub 2022 Jan 6.
- Results publication: PubMed 30635612Pak HH, Cummings NE, Green CL, Brinkman JA, Yu D, Tomasiewicz JL, Yang SE, Boyle C, Konon EN, Ong IM, Lamming DW. The Metabolic Response to a Low Amino Acid Diet is Independent of Diet-Induced Shifts in the Composition of the Gut Microbiome. Sci Rep. 2019 Jan 11;9(1):67. doi: 10.1038/s41598-018-37177-3.
- Results publication: PubMed 31019023Tirosh A, Calay ES, Tuncman G, Claiborn KC, Inouye KE, Eguchi K, Alcala M, Rathaus M, Hollander KS, Ron I, Livne R, Heianza Y, Qi L, Shai I, Garg R, Hotamisligil GS. The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans. Sci Transl Med. 2019 Apr 24;11(489):eaav0120. doi: 10.1126/scitranslmed.aav0120.
- Results publication: PubMed 26757816Kumar DP, Asgharpour A, Mirshahi F, Park SH, Liu S, Imai Y, Nadler JL, Grider JR, Murthy KS, Sanyal AJ. Activation of Transmembrane Bile Acid Receptor TGR5 Modulates Pancreatic Islet alpha Cells to Promote Glucose Homeostasis. J Biol Chem. 2016 Mar 25;291(13):6626-40. doi: 10.1074/jbc.M115.699504. Epub 2016 Jan 12.
- Results publication: PubMed 26154278Murphy EA, Velazquez KT, Herbert KM. Influence of high-fat diet on gut microbiota: a driving force for chronic disease risk. Curr Opin Clin Nutr Metab Care. 2015 Sep;18(5):515-20. doi: 10.1097/MCO.0000000000000209.
- Results publication: PubMed 28388917Singh RK, Chang HW, Yan D, Lee KM, Ucmak D, Wong K, Abrouk M, Farahnik B, Nakamura M, Zhu TH, Bhutani T, Liao W. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017 Apr 8;15(1):73. doi: 10.1186/s12967-017-1175-y.
- Results publication: PubMed 32408110Wei M, Huang F, Zhao L, Zhang Y, Yang W, Wang S, Li M, Han X, Ge K, Qu C, Rajani C, Xie G, Zheng X, Zhao A, Bian Z, Jia W. A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility. EBioMedicine. 2020 May;55:102766. doi: 10.1016/j.ebiom.2020.102766. Epub 2020 May 11.
- Results publication: PubMed 35276812Wu S, Bhat ZF, Gounder RS, Mohamed Ahmed IA, Al-Juhaimi FY, Ding Y, Bekhit AEA. Effect of Dietary Protein and Processing on Gut Microbiota-A Systematic Review. Nutrients. 2022 Jan 20;14(3):453. doi: 10.3390/nu14030453.
- Results publication: PubMed 13428781FOLCH J, LEES M, SLOANE STANLEY GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497-509. No abstract available.
- Results publication: PubMed 15556534Keller S, Jahreis G. Determination of underivatised sterols and bile acid trimethyl silyl ether methyl esters by gas chromatography-mass spectrometry-single ion monitoring in faeces. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Dec 25;813(1-2):199-207. doi: 10.1016/j.jchromb.2004.09.046.
- 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.
Maria del Rocio Guizar-Heredia, Master study chair
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran
Armando R Tovar, Doctor principal investigator
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran
Martha Guevara-Cruz, Doctor study director
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-protein diet in people with Healthy, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 1 site in Mexico.
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 5 inclusion and 19 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 5 Mar 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 Mexico. 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 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?
Changes in faecal microbiota composition in response to high-protein diet (time frame: baseline, 7 days and 14 days). The study lists 2 primary outcomes in all. 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 NCT05906641, which also lists 13 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 5 Mar 2024.