Acid Base DisorderNCT01880281
Effect of the Diet on Urinary Excretion of Alpha-ketoglutarate
A study testing Meat and vegetable diet in people with Acid Base Disorder, run by Michel Burnier at 1 site in Switzerland.
Trial summary
The G coupled-protein receptors 99 (GPR99) was discovered in 2002 by Wittenberg et al. and is involved as a metabolic receptor. It has been shown that the natural ligand of GPR99 is an intermediate in the Krebs cycle, alpha-ketoglutarate (aKG). Read more about this study
- Who is it for?
- Ages 18 to 44 yearsHealthy volunteers can take part
- Conditions the study is for
- Acid Base Disorder
- What is being tested?
- Meat and vegetable diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jun 2013to Jul 2015
- 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 to 44 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy person
- Age >or= 18, <45
- Caucasian
- Non-smoker
- BMI >or= 18, <25
- normal physical examination
Show all 12Show fewer
- normal ECG 12 pistes
- systolic blood pressure <or= 139 mmHg and diastolic blood pressure <or= 89 mmHG (after 5 minutes lying, 3 measures a 2-minutes interval, left arm)
- Heart rate <or= 90
- Person can understand the written information and the written consent
- Person gave his/her written consent with date and signature before the start of the study
- Urinary pH > or = 6.5 in the fist urine of the day ( for vegetarian / vegan volunteers only)
Who cannot join
- vegetarian or vegan diet ( for omnivorous volunteers only)
- electrolytic disorder defined by Na, K, total calcium, phosphate out of the reference's values of laboratory
- seropositive for HIV, HBV or HCV
- Positive for drugs detected in urine (opiates, cannabinoids, cocaine, benzodiazepines, amphetamines, barbiturates)
- fall of systolic or diastolic blood pressure > 10mmHg after one minute standing or all other postural hypotension
- any clinically significant disease or condition at gastrointestinal, respiratory, psychiatric, neurological, renal, hepatic, cardiac and other physical sign abnormality which can interfere with the study
Show all 10Show fewer
- Pregnant during the screening
- current participation or less than 60 days before the screening to another investigational study
- chronic use of any drug during the 4 weeks preceding the inclusion visit (paracetamol excepted)
- donation of blood, platelets, plasma or bone marrow within 3 months preceding the inclusion visit
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Service de néphrologie, Centre Hospitalier Universitaire Vaudois
Lausanne, Canton of Vaud, 1011
About this study
Official title: Effect of a Meat Versus Vegetarian Diet in 12 Healthy Volunteers on the Excretion of Alpha-ketoglutarate Measured in 24-hours Urine
- The G coupled-protein receptors 99 (GPR99) was discovered in 2002 by Wittenberg et al. and is involved as a metabolic receptor. It has been shown that the natural ligand of GPR99 is an intermediate in the Krebs cycle, alpha-ketoglutarate (aKG). Studies done on rats have shown that aKG is measurable in the blood, freely filtered by the glomerulus and highly reabsorbed in the proximal tubule in metabolic acidosis, while it is not reabsorbed in metabolic alkalosis. No absorption or secretion of aKG intervene between the end of the proximal tubule and the final urine. Thus, having a receptor aKG in the distal tubule creates a paracrine communication with the proximal tubule, informing about the acid-base status of the body and allows adjustment of the urinary excretion of acid or base.
- The hypothesis is that GPR99 is aKG sensor in the distal tubules and allow to report the acid-base status (determined by the metabolic activity of the proximal tubule) of the body to the distal tubule. This can then adapt the urinary excretion of acid or base in the final urine. Acidifying the body by a high meat consumption associated with a test of acidification, the kidney should reduce its aKG excretion and the concentration of this metabolite should be even lower in the urine. And vice versa in the case of alkalizing the body through a vegetarian diet associated with an alkalizing test.
- Twelve healthy omnivorous volunteers will be selected. First inclusion visit includes verification of inclusion/exclusion criteria and signed informed consent. Urine and plasma baseline measurements will be performed and volunteers will meet a dietician. This person will tell them concerning meat and vegetarian diet as well as how to have a diet with 6g of salt per day.Volunteers are then randomized in order to determine which diet they will start first.The first phase will last during 4 days. The diet is followed during 3 days, and a 24-hour urine collection will begin on the third day at 7: 00 am. The fourth day, volunteers will have an investigational's day at the investigation's center after completing their urine collection at home (7:00 am). During the day of investigation, volunteers will give their urine (8: 00 am, corresponding to the baseline urine), and then the "meat" arm will receive a tablet of 50meq of NH4Cl and the "vegetarian" arm will receive a tablet of 1g of NaHC03. Volunteers will stay in the investigation center for 6h. Each hour since 8:00am, a urine sample will be taken, and at 3 hours and 6 hours post-tablet, a blood sample will also be made.This investigational's day will be followed by one to two weeks of treatment washing out. After that, the second phase will begin and will as the first phase excepted that the diet will be inversed. 5 other healthy vegetarian or vegan volunteers are recruited. Inclusion visit is the same as omnivorous volunteers. Only investigational's day at the investigation's center will be performed (no diet, no urine collection).
- Conditions
- Acid Base Disorder
- Being tested
- Meat and vegetable diet
- Keywords
- G protein-coupled receptor 99, 2-oxoglutarate receptor 1, alpha-ketoglutarate, urine, pH, acidosis, alkalosis, Healthy volunteers
- Medical subject headings
- Acidosis, Alkalosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Meat and vegetable dietOther
After having a diet of 3 days and the investigational's day, the volunteers will have the other diet
| Study group | Role | What they receive |
|---|---|---|
| Meat diet without any vegetables or fruits | Active comparator | The volunteers will follow a diet of 3 days with at least 400g of meat per day. The 3rd day, the volunteers will do a collect of 24-hour urine.
The investigational's day, they will receive 50meq of ammonium chlorid over a period of one hour in order to avoid the effect of nausea. Receives: Other: Meat and vegetable diet |
| Vegetarian diet without any sources of protein | Active comparator | The volunteers will follow a diet of 3 days with at least 600g of fruits and vegetables per day without any proteins (animal or vegetal like soybean). The 3rd day, the volunteers will do a collect of 24-hour urine.
The investigational's day, they will receive 1g of bicarbonate. Receives: Other: Meat and vegetable diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
urinary concentration of alpha-ketoglutarate + plasmatic and urinary pH
alpha-ketoglutarate measured by titration pH measured by pH-metry
Measured: up to two investigational's day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionMar 2014
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Acid Base DisorderStudies 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michel Burnier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Michel Burnier, Centre Hospitalier Universitaire Vaudois
- Investigators
- Michel Burnier, professor, Principal investigator, Centre Hospitalier Universitaire Vaudois
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01880281
- Sponsor's protocol ID
- 134/13
- Status last verified
- Jul 2019
- First submitted
- 14 Jun 2013
- Last updated
- 31 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Wittenberger T, Hellebrand S, Munck A, Kreienkamp HJ, Schaller HC, Hampe W. GPR99, a new G protein-coupled receptor with homology to a new subgroup of nucleotide receptors. BMC Genomics. 2002 Jul 5;3:17. doi: 10.1186/1471-2164-3-17. Epub 2002 Jul 5.
PubMed 12098360Gonzalez NS, Communi D, Hannedouche S, Boeynaems JM. The fate of P2Y-related orphan receptors: GPR80/99 and GPR91 are receptors of dicarboxylic acids. Purinergic Signal. 2004 Dec;1(1):17-20. doi: 10.1007/s11302-004-5071-6.
PubMed 18404396Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Miras-Portugal MT, King BF, Gachet C, Jacobson KA, Weisman GA. The recently deorphanized GPR80 (GPR99) proposed to be the P2Y15 receptor is not a genuine P2Y receptor. Trends Pharmacol Sci. 2005 Jan;26(1):8-9. doi: 10.1016/j.tips.2004.10.010. No abstract available.
PubMed 15629198He W, Miao FJ, Lin DC, Schwandner RT, Wang Z, Gao J, Chen JL, Tian H, Ling L. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature. 2004 May 13;429(6988):188-93. doi: 10.1038/nature02488.
PubMed 15141213Tokonami N, Morla L, Centeno G, Mordasini D, Ramakrishnan SK, Nikolaeva S, Wagner CA, Bonny O, Houillier P, Doucet A, Firsov D. alpha-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism. J Clin Invest. 2013 Jul;123(7):3166-71. doi: 10.1172/JCI67562. Epub 2013 Jun 24.
PubMed 23934124
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of a Meat Versus Vegetarian Diet in 12 Healthy Volunteers on the Excretion of Alpha-ketoglutarate Measured in 24-hours Urine
- ClinicalTrials.gov ID
- NCT01880281
- Acronym / sponsor ID
- 134/13
- Conditions
- Acid Base Disorder
- Keywords
- G protein-coupled receptor 99, 2-oxoglutarate receptor 1, alpha-ketoglutarate, urine, pH, acidosis, alkalosis, Healthy volunteers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Michel BurnierUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Mar 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 18 Jun 2013 (estimated)
- 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.
- The G coupled-protein receptors 99 (GPR99) was discovered in 2002 by Wittenberg et al. and is involved as a metabolic receptor. It has been shown that the natural ligand of GPR99 is an intermediate in the Krebs cycle, alpha-ketoglutarate (aKG). Studies done on rats have shown that aKG is measurable in the blood, freely filtered by the glomerulus and highly reabsorbed in the proximal tubule in metabolic acidosis, while it is not reabsorbed in metabolic alkalosis. No absorption or secretion of aKG intervene between the end of the proximal tubule and the final urine. Thus, having a receptor aKG in the distal tubule creates a paracrine communication with the proximal tubule, informing about the acid-base status of the body and allows adjustment of the urinary excretion of acid or base.
- The hypothesis is that GPR99 is aKG sensor in the distal tubules and allow to report the acid-base status (determined by the metabolic activity of the proximal tubule) of the body to the distal tubule. This can then adapt the urinary excretion of acid or base in the final urine. Acidifying the body by a high meat consumption associated with a test of acidification, the kidney should reduce its aKG excretion and the concentration of this metabolite should be even lower in the urine. And vice versa in the case of alkalizing the body through a vegetarian diet associated with an alkalizing test.
- Twelve healthy omnivorous volunteers will be selected. First inclusion visit includes verification of inclusion/exclusion criteria and signed informed consent. Urine and plasma baseline measurements will be performed and volunteers will meet a dietician. This person will tell them concerning meat and vegetarian diet as well as how to have a diet with 6g of salt per day.Volunteers are then randomized in order to determine which diet they will start first.The first phase will last during 4 days. The diet is followed during 3 days, and a 24-hour urine collection will begin on the third day at 7: 00 am. The fourth day, volunteers will have an investigational's day at the investigation's center after completing their urine collection at home (7:00 am). During the day of investigation, volunteers will give their urine (8: 00 am, corresponding to the baseline urine), and then the "meat" arm will receive a tablet of 50meq of NH4Cl and the "vegetarian" arm will receive a tablet of 1g of NaHC03. Volunteers will stay in the investigation center for 6h. Each hour since 8:00am, a urine sample will be taken, and at 3 hours and 6 hours post-tablet, a blood sample will also be made.This investigational's day will be followed by one to two weeks of treatment washing out. After that, the second phase will begin and will as the first phase excepted that the diet will be inversed. 5 other healthy vegetarian or vegan volunteers are recruited. Inclusion visit is the same as omnivorous volunteers. Only investigational's day at the investigation's center will be performed (no diet, no urine collection).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Meat diet without any vegetables or fruits | Active comparator | Other: Meat and vegetable dietThe volunteers will follow a diet of 3 days with at least 400g of meat per day. The 3rd day, the volunteers will do a collect of 24-hour urine. The investigational's day, they will receive 50meq of ammonium chlorid over a period of one hour in order to avoid the effect of nausea. |
| Vegetarian diet without any sources of protein | Active comparator | Other: Meat and vegetable dietThe volunteers will follow a diet of 3 days with at least 600g of fruits and vegetables per day without any proteins (animal or vegetal like soybean). The 3rd day, the volunteers will do a collect of 24-hour urine. The investigational's day, they will receive 1g of bicarbonate. |
Who may qualify
- Ages
- 18 to 44 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- healthy person
- Age >or= 18, <45
- Caucasian
- Non-smoker
- BMI >or= 18, <25
Key exclusion criteria (10 listed)
- vegetarian or vegan diet ( for omnivorous volunteers only)
- electrolytic disorder defined by Na, K, total calcium, phosphate out of the reference's values of laboratory
- seropositive for HIV, HBV or HCV
- Positive for drugs detected in urine (opiates, cannabinoids, cocaine, benzodiazepines, amphetamines, barbiturates)
- fall of systolic or diastolic blood pressure > 10mmHg after one minute standing or all other postural hypotension
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 |
|---|---|---|
| Meat and vegetable dietAfter having a diet of 3 days and the investigational's day, the volunteers will have the other diet | Other | Meat diet without any vegetables or fruits, Vegetarian diet without any sources of protein |
Primary outcome
urinary concentration of alpha-ketoglutarate + plasmatic and urinary pH
Time frame: up to two investigational's day
alpha-ketoglutarate measured by titration pH measured by pH-metry
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 31 Jul 2019.
- Background: PubMed 12098360Wittenberger T, Hellebrand S, Munck A, Kreienkamp HJ, Schaller HC, Hampe W. GPR99, a new G protein-coupled receptor with homology to a new subgroup of nucleotide receptors. BMC Genomics. 2002 Jul 5;3:17. doi: 10.1186/1471-2164-3-17. Epub 2002 Jul 5.
- Background: PubMed 18404396Gonzalez NS, Communi D, Hannedouche S, Boeynaems JM. The fate of P2Y-related orphan receptors: GPR80/99 and GPR91 are receptors of dicarboxylic acids. Purinergic Signal. 2004 Dec;1(1):17-20. doi: 10.1007/s11302-004-5071-6.
- Background: PubMed 15629198Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Miras-Portugal MT, King BF, Gachet C, Jacobson KA, Weisman GA. The recently deorphanized GPR80 (GPR99) proposed to be the P2Y15 receptor is not a genuine P2Y receptor. Trends Pharmacol Sci. 2005 Jan;26(1):8-9. doi: 10.1016/j.tips.2004.10.010. No abstract available.
- Background: PubMed 15141213He W, Miao FJ, Lin DC, Schwandner RT, Wang Z, Gao J, Chen JL, Tian H, Ling L. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature. 2004 May 13;429(6988):188-93. doi: 10.1038/nature02488.
- Background: PubMed 23934124Tokonami N, Morla L, Centeno G, Mordasini D, Ramakrishnan SK, Nikolaeva S, Wagner CA, Bonny O, Houillier P, Doucet A, Firsov D. alpha-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism. J Clin Invest. 2013 Jul;123(7):3166-71. doi: 10.1172/JCI67562. Epub 2013 Jun 24.
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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.
Michel Burnier, professor principal investigator
Centre Hospitalier Universitaire Vaudois
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Meat and vegetable diet in people with Acid Base Disorder, run by Michel Burnier at 1 site in Switzerland.
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 12 inclusion and 10 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 31 Jul 2019. 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 Switzerland. 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?
urinary concentration of alpha-ketoglutarate + plasmatic and urinary pH (time frame: up to two investigational's day). 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 NCT01880281, which also lists 5 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 31 Jul 2019.