Metabolic DiseasePROCAL2NCT04659902
Protein, Calcium and Gut Hormone Secretion
A study testing Protein form in people with Metabolic Disease, run by University of Bath at 1 site in United Kingdom.
Trial summary
Hormones that are produced by our stomach and intestines play a role in regulating our appetite and health, and are therefore of high interest for managing conditions such as obesity and Type 2 Diabetes (T2D). Two important hormones, called GLP-1 and PYY, are released from the same intestinal cell. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Metabolic Disease
- What is being tested?
- Protein form
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Dec 2020to 1 Oct 2021
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index 18.5-25.0 kg∙m-2
- Age 18-65 years
- Able and willing to provide informed consent and safely comply with study procedures
- Females to maintain record of regular menstrual cycle phase or contraceptive use
- No anticipated changes in diet/physical activity during the study (e.g. holidays or diet plans)
Who cannot join
- Allergies or adverse reactions to calcium or milk proteins.
- Contradictions to a high intake of calcium e.g. history of kidney stones
- Any reported condition or behaviour deemed either to pose undue personal risk to the participant or introduce bias
- Any diagnosed gastrointestinal or metabolic disease (e.g. type 1 or type 2 diabetes)
- Any reported use of substances which may pose undue personal risk to the participants or introduce bias into the experiment
- Lifestyle not conforming to standard sleep-wake cycle (e.g. shift worker)
- Any reported recent (<6 months) change in body mass (± 3%)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Department For Health, University of Bath
Bath, Somerset, BA2 7AY
About this study
Official title: The Influence of Protein Form and the Presence or Absence of Calcium on Gut Hormone Secretion and Gastric Emptying in Lean Healthy Individuals
Hormones that are produced by our stomach and intestines play a role in regulating our appetite and health, and are therefore of high interest for managing conditions such as obesity and Type 2 Diabetes (T2D). Two important hormones, called GLP-1 and PYY, are released from the same intestinal cell. The food we eat influences the release of these hormone and evidence suggests that protein and calcium are key nutrients that stimulate the secretion of GLP-1, while the influence of this combination on PYY release is less clear. Furthermore, gastric emptying affects the rate of absorption of nutrients and by manipulating the structural form of protein, in the absence or presence of calcium, we may be able to learn more about the processes mediating the gut hormone response. We hypothesise that gut hormone secretion will be enhanced following the ingestion of a partially digested protein in the presence of calcium versus a control protein without calcium. Additionally, the ingestion of the partially digested protein will result in faster gastric emptying compared to the control protein.
Read the detailed description
Recent work at the University of Bath has shown that when ingested with 50 g whey protein hydrolysate, Capolac® (milk minerals high in calcium) potently stimulates availability of the important hormone glucagon-like peptide-1 (GLP-1). However, it is currently unclear how the form of protein ingested with the presence or absence of calcium may affect gut hormone secretion and gastric emptying. Therefore we aim to perform a study on the effect of co-ingesting two different forms of protein in the presence or absence of calcium on gut hormone availability and gastric emptying. This project will help provide key evidence to aid future work and recommendations for nutrition-based interventions for the prevention and management of obesity and T2D.
Fifteen metabolically healthy men and women, age 18-65 years, BMI between 18.5 and 25 kg/m2 will be recruited to participate in a randomised crossover study. Each participant will undergo 4 trials. Each trial will last ~3 hours and will be separated by a minimum of 48h:
CONTROL (CON) - 30 g Control protein only CONTROL + CALCIUM (CON-C) - 30 g Control protein + 9547 mg Capolac® (2500 mg of calcium ingested) PROTEIN (PRO) - 30 g Aggregate protein only PROTEIN + CALCIUM (PRO-C) - 30 g Aggregate protein + 9547 mg Capolac® (2500 mg of calcium ingested)
Each of these drinks will also contain 500 mL of water, low calorie sweetener (80 mg sucralose) and will be labelled with 150 mg 13C1 sodium acetate, and 100 mg 13C1 sodium octanoate for the measurement of gastric emptying.
Participants will be asked to arrive to the laboratory between 09:00 and 10:00 am after not eating for between 10-14 hours i.e. in a fasted state (water intake is permitted and encouraged). Upon arrival at the laboratory a trained phlebotomist staff member will insert a cannula (a small plastic tube) into a pre-heated dorsal hand vein on the back of the hand, or if unsuccessful, the antecubital vein. Participants will then be given one of the four test drinks, which once ingested will initiate the trial. Just after the ingestion of the test drink we will ask participants to fill out a palatability scale.
Blood samples will be taken at baseline, and at 15, 30, 45, 60, 90, and 120 minutes after ingestion of the test drink. Breath samples will be collected in exetainers at baseline, and every 5 minutes until the 120-minute time point to determine gastric emptying. An appetite questionnaire will also be completed at baseline and every 60 minutes after ingestion of the test drink to assess appetite sensations. After the 120-minute time point participants will be asked to consume a lunch meal until they are comfortably full. Once satisfied with the lunch meal they will fill out the final appetite questionnaire. The trial day will then be complete. Following study completion participants will be asked to complete a restrained eating questionnaire.
A subset of 5 participants will be fitted with a nasogastric tube by a qualified BAPEN nurse. 5ml aspirate from the stomach will be samples at baseline, 30, 60, and 120 minutes which will be distributed equally for analyte profiling and in vitro culture work. 3 ml gastric aspirate will be used to stimulate a GLUTag cell line. Experiments will be performed by incubating cells with the neutralised gastric aspirate in 250 µl Krebs Ringer Buffer (KRB) for 2 h at 37˚C, 5 % CO2. A second culture, identical to that previously described will be conducted, only with the addition of specific cell receptor antagonists.
- Conditions
- Metabolic Disease
- Being tested
- Protein form
- Medical subject headings
- Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protein formDietary supplement
Protein form and absence or presence of calcium manipulated
| Study group | Role | What they receive |
|---|---|---|
| CON | Placebo comparator | Participants will ingest a drink containing a control protein only Receives: Dietary Supplement: Protein form |
| CON-C | Active comparator | Participants will ingest a drink containing a control protein plus Capolac® (9547 mg to provide 2500mg of calcium) Receives: Dietary Supplement: Protein form |
| PRO | Active comparator | Participants will ingest a drink containing an aggregate protein only Receives: Dietary Supplement: Protein form |
| PRO-C | Active comparator | Participants will ingest a drink containing an aggregate protein plus Capolac® (9547 mg to provide 2500mg of calcium) Receives: Dietary Supplement: Protein form |
What is being measured
The primary outcome is the main question the study is designed to answer.
incremental area under the curve (iAUC) for total plasma GLP-1
Blood sampling
Measured: 2 hours
Secondary outcomes (10)
Gastric emptying
gastric emptying measured via acetate breath test
Measured: 2 hours
in vitro gut hormone secretion
GLP-1 and peptide tyrosine tyrosine (PYY) secretion from GLUTag cell line
Measured: 2 hours
iAUC for total PYY
Blood sampling
Measured: 2 hours
iAUC for plasma and gastric amino acid profile
blood and gastric sampling
Measured: 2 hours
iAUC for plasma Dipeptidyl Peptidase-IV (DPP4)
blood sampling
Measured: 2 hours
iAUC for plasma insulin
blood sampling
Measured: 2 hours
iAUC for plasma glucose
blood sampling
Measured: 2 hours
iAUC for active plasma GLP-1
blood sampling
Measured: 2 hours
Visual appetite scales
4 questions to measure subjective appetite, hunger, fullness and prospective consumption, participant marks where they feel they are on a continuum from one extreme to another e.g. i have never been so hungry to i have never been more hungry
Measured: 2 hours
ad libitum lunch meal
a pasta lunch meal is provided where the participant eats as much as they want until they are comfortably full, energy intake is measured
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2020
- Study start1 Dec 2020
- Primary completion1 Oct 2021
- Study completion1 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metabolic DiseaseStudies 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
- Model description
- There are 4 conditions where participants will ingest different forms of protein in the presence or absence of calcium.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Bath
- Sponsor type
- University, hospital or other
- Collaborators
- Arla Foods
- Responsible party
- Principal investigator, Jonathan Watkins, University of Bath
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04659902
- Sponsor's protocol ID
- PROCAL2-JW
- Acronym
- PROCAL2
- Status last verified
- Aug 2022
- First submitted
- 1 Dec 2020
- Last updated
- 16 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Watkins JD, Smith HA, Hengist A, Nielsen SB, Mikkelsen UR, Saunders J, Koumanov F, Betts JA, Gonzalez JT. Effects of physical form of beta-lactoglobulin and calcium ingestion on GLP-1 secretion, gastric emptying and energy intake in humans: a randomised crossover trial. Br J Nutr. 2024 May 28;131(10):1730-1739. doi: 10.1017/S0007114524000321. Epub 2024 Jan 30.
PubMed 38287700
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Protein Form and the Presence or Absence of Calcium on Gut Hormone Secretion and Gastric Emptying in Lean Healthy Individuals
- ClinicalTrials.gov ID
- NCT04659902
- Acronym / sponsor ID
- PROCAL2 / PROCAL2-JW
- Conditions
- Metabolic Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of BathUniversity, hospital or other
- Collaborators
- Arla Foods
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 1 Oct 2021 (actual)
- Study completion
- 1 Oct 2021 (actual)
- First posted
- 9 Dec 2020 (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.
Hormones that are produced by our stomach and intestines play a role in regulating our appetite and health, and are therefore of high interest for managing conditions such as obesity and Type 2 Diabetes (T2D). Two important hormones, called GLP-1 and PYY, are released from the same intestinal cell. The food we eat influences the release of these hormone and evidence suggests that protein and calcium are key nutrients that stimulate the secretion of GLP-1, while the influence of this combination on PYY release is less clear. Furthermore, gastric emptying affects the rate of absorption of nutrients and by manipulating the structural form of protein, in the absence or presence of calcium, we may be able to learn more about the processes mediating the gut hormone response. We hypothesise that gut hormone secretion will be enhanced following the ingestion of a partially digested protein in the presence of calcium versus a control protein without calcium. Additionally, the ingestion of the partially digested protein will result in faster gastric emptying compared to the control protein.
Detailed description
Recent work at the University of Bath has shown that when ingested with 50 g whey protein hydrolysate, Capolac® (milk minerals high in calcium) potently stimulates availability of the important hormone glucagon-like peptide-1 (GLP-1). However, it is currently unclear how the form of protein ingested with the presence or absence of calcium may affect gut hormone secretion and gastric emptying. Therefore we aim to perform a study on the effect of co-ingesting two different forms of protein in the presence or absence of calcium on gut hormone availability and gastric emptying. This project will help provide key evidence to aid future work and recommendations for nutrition-based interventions for the prevention and management of obesity and T2D.
Fifteen metabolically healthy men and women, age 18-65 years, BMI between 18.5 and 25 kg/m2 will be recruited to participate in a randomised crossover study. Each participant will undergo 4 trials. Each trial will last ~3 hours and will be separated by a minimum of 48h:
CONTROL (CON) - 30 g Control protein only CONTROL + CALCIUM (CON-C) - 30 g Control protein + 9547 mg Capolac® (2500 mg of calcium ingested) PROTEIN (PRO) - 30 g Aggregate protein only PROTEIN + CALCIUM (PRO-C) - 30 g Aggregate protein + 9547 mg Capolac® (2500 mg of calcium ingested)
Each of these drinks will also contain 500 mL of water, low calorie sweetener (80 mg sucralose) and will be labelled with 150 mg 13C1 sodium acetate, and 100 mg 13C1 sodium octanoate for the measurement of gastric emptying.
Participants will be asked to arrive to the laboratory between 09:00 and 10:00 am after not eating for between 10-14 hours i.e. in a fasted state (water intake is permitted and encouraged). Upon arrival at the laboratory a trained phlebotomist staff member will insert a cannula (a small plastic tube) into a pre-heated dorsal hand vein on the back of the hand, or if unsuccessful, the antecubital vein. Participants will then be given one of the four test drinks, which once ingested will initiate the trial. Just after the ingestion of the test drink we will ask participants to fill out a palatability scale.
Blood samples will be taken at baseline, and at 15, 30, 45, 60, 90, and 120 minutes after ingestion of the test drink. Breath samples will be collected in exetainers at baseline, and every 5 minutes until the 120-minute time point to determine gastric emptying. An appetite questionnaire will also be completed at baseline and every 60 minutes after ingestion of the test drink to assess appetite sensations. After the 120-minute time point participants will be asked to consume a lunch meal until they are comfortably full. Once satisfied with the lunch meal they will fill out the final appetite questionnaire. The trial day will then be complete. Following study completion participants will be asked to complete a restrained eating questionnaire.
A subset of 5 participants will be fitted with a nasogastric tube by a qualified BAPEN nurse. 5ml aspirate from the stomach will be samples at baseline, 30, 60, and 120 minutes which will be distributed equally for analyte profiling and in vitro culture work. 3 ml gastric aspirate will be used to stimulate a GLUTag cell line. Experiments will be performed by incubating cells with the neutralised gastric aspirate in 250 µl Krebs Ringer Buffer (KRB) for 2 h at 37˚C, 5 % CO2. A second culture, identical to that previously described will be conducted, only with the addition of specific cell receptor antagonists.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- There are 4 conditions where participants will ingest different forms of protein in the presence or absence of calcium.
| Arm | Type | Receives |
|---|---|---|
| CON | Placebo comparator | Dietary Supplement: Protein formParticipants will ingest a drink containing a control protein only |
| CON-C | Active comparator | Dietary Supplement: Protein formParticipants will ingest a drink containing a control protein plus Capolac® (9547 mg to provide 2500mg of calcium) |
| PRO | Active comparator | Dietary Supplement: Protein formParticipants will ingest a drink containing an aggregate protein only |
| PRO-C | Active comparator | Dietary Supplement: Protein formParticipants will ingest a drink containing an aggregate protein plus Capolac® (9547 mg to provide 2500mg of calcium) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Body mass index 18.5-25.0 kg∙m-2
- Age 18-65 years
- Able and willing to provide informed consent and safely comply with study procedures
- Females to maintain record of regular menstrual cycle phase or contraceptive use
- No anticipated changes in diet/physical activity during the study (e.g. holidays or diet plans)
Key exclusion criteria (7 listed)
- Allergies or adverse reactions to calcium or milk proteins.
- Contradictions to a high intake of calcium e.g. history of kidney stones
- Any reported condition or behaviour deemed either to pose undue personal risk to the participant or introduce bias
- Any diagnosed gastrointestinal or metabolic disease (e.g. type 1 or type 2 diabetes)
- Any reported use of substances which may pose undue personal risk to the participants or introduce bias into the experiment
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 |
|---|---|---|
| Protein formProtein form and absence or presence of calcium manipulated | Dietary supplement | CON, CON-C, PRO, PRO-C |
Primary outcome
incremental area under the curve (iAUC) for total plasma GLP-1
Time frame: 2 hours
Blood sampling
10 secondary outcomes
Gastric emptying
Time frame: 2 hours
in vitro gut hormone secretion
Time frame: 2 hours
iAUC for total PYY
Time frame: 2 hours
iAUC for plasma and gastric amino acid profile
Time frame: 2 hours
iAUC for plasma Dipeptidyl Peptidase-IV (DPP4)
Time frame: 2 hours
iAUC for plasma insulin
Time frame: 2 hours
iAUC for plasma glucose
Time frame: 2 hours
iAUC for active plasma GLP-1
Time frame: 2 hours
Visual appetite scales
Time frame: 2 hours
ad libitum lunch meal
Time frame: 2 hours
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 16 Aug 2022.
- Derived from this study: PubMed 38287700Watkins JD, Smith HA, Hengist A, Nielsen SB, Mikkelsen UR, Saunders J, Koumanov F, Betts JA, Gonzalez JT. Effects of physical form of beta-lactoglobulin and calcium ingestion on GLP-1 secretion, gastric emptying and energy intake in humans: a randomised crossover trial. Br J Nutr. 2024 May 28;131(10):1730-1739. doi: 10.1017/S0007114524000321. Epub 2024 Jan 30.
- 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 Protein form in people with Metabolic Disease, run by University of Bath at 1 site in United Kingdom.
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 7 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 16 Aug 2022. 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 Kingdom. 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. Some participants in this study may receive a placebo. 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?
incremental area under the curve (iAUC) for total plasma GLP-1 (time frame: 2 hours). 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 NCT04659902, which also lists 1 linked publication.
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 16 Aug 2022.