Dietary ExposureHiProLepNCT05002491
Change in Leptin as a Predictor of Satiety With High Protein Feeding
A study testing High protein diet in people with Dietary Exposure, run by Oregon Health and Science University.
Trial summary
Body weight can be affected by the content of fat and carbohydrate in the diet. On average, people will lose a modest (< 5 kg) amount of weight when switched from a high fat diet to a low fat, high carbohydrate diet. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Dietary Exposure
- What is being tested?
- High protein diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2002to 31 Dec 2003
- 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
- Adult, Older adult
Who may be able to join
- Ability to provide informed written consent
- Age between 18 and 65 years
- Willingness to consume only food prepared by the CRC for 6 weeks
- Body mass index between 22 and 28 kg/m2
- Weight stable to within 2 kg for 3 months preceding study, and at lifetime maximal weight
Who cannot join
- Diabetes mellitus
- Renal disease
- Other chronic medical or psychiatric illness
- Pregnancy or female subject unwilling to use contraception
- Use of tobacco products
- Regular intense exercise (>30 minutes of aerobics, 3x / week)
Show all 9Show fewer
- Vegetarian or extreme dietary preferences (< 20% or > 40% fat diet, > 40% protein diet)
- Use of anabolic steroids, glucocorticoids, or lipid-lowering agents
- Alcohol consumption >2 drinks / day
About this study
Body weight can be affected by the content of fat and carbohydrate in the diet. On average, people will lose a modest (< 5 kg) amount of weight when switched from a high fat diet to a low fat, high carbohydrate diet. Determining mechanisms whereby changing the makeup of the diet can change one's body weight will be important in understanding why body weight in the US population is trending upward recently and what health care providers can recommend to reverse this trend. Previous studies have shown that increasing the carbohydrate and lowering the fat content in the diet leads to a change in the appearance of the hormone leptin in the blood over 24 hours. Leptin is an important signal from the fat cell to the brain that leads to a reduction in appetite and weight loss. A previous study found that after keeping people's weight stable, that the greater rise in leptin over the day on a low fat-high carbohydrate diet compared to a high fat diet predicted the reduction in calories they ate over a subsequent 12 weeks when their weight was allowed to freely fluctuate. Recent studies have also provided evidence that limiting fat and increasing the amount of protein in the diet also leads to modest weight loss. It is therefore proposed to test whether low fat, high protein diets also result a change in leptin secretion, and if this change predicts a reduction in appetite when they are allowed to eat freely.
Read the detailed description
The role of leptin in regulating body fat mass in humans is incompletely understood. Although complete loss of leptin signaling results in morbid obesity, there is an inconsistent association between more subtle changes in leptin levels and changes in body composition. Administration of recombinant leptin to human volunteers also results in a variable loss of fat mass. Therapeutic high carbohydrate diets generally lead to decreased caloric intake and weight loss compared with high fat diets. The mechanism of this decrease in appetite is, however, unknown. In preliminary data, the invesigators have shown that compared to high fat feeding, isocaloric high carbohydrate feeding over 2 weeks leads to increased leptin excursion during 24 hours. In addition, this change in leptin signaling predicts subsequent reduction in daily caloric intake with ad-lib high carbohydrate feeding. It has recently been reported that an increase in dietary protein also leads to modest spontaneous weight loss in ad-lib feeding subjects. The current proposal is to therefore determine whether prolonged high protein feeding leads to a sustained increase in the integrated daily leptin level and whether this increase predicts a subsequent decrease in caloric intake in human volunteers. Eligible subjects will consume a control protein diet (15%, low protein) followed by a high protein diet (30% protein) for 2 weeks each while maintaining weight stability. At the end of each 2-week feeding phase, subjects will be admitted to the inpatient GCRC for frequent sampling for insulin and leptin levels over 24 hours. Immediately following the second CRC inpatient visit, subjects will continue to consume the high protein diet ad-libitum for another 12 weeks, during which time they will be followed for changes in their caloric intake and body weight. Because of limitations in metabolic kitchen resources, if this study were to be conducted solely at OHSU, it would require recruitment and study of two groups of subjects over sequential time periods. This results in delay of acquisition of data, completion of the study, and the potential introduction of seasonal variation as a study confounder. Therefore, a two-site study is proposed utilizing the metabolic kitchen resources of OHSU and the University of Washington GCRC's jointly. Instead of two groups of subjects being recruited and studied sequentially at one site, subjects will be recruited at both sites and studied in parallel, thus allowing the completion of the protocol in half the usual amount of time and without additional study confounders.
It is hypothesized that switching human volunteers from a 15% protein diet to an isocaloric high (30%) protein diet will cause a significant increase in the area under the diurnal plasma leptin versus time curve (AUC-leptin) and the insulin versus time curve (AUC-insulin), that these increases will be sustained over 2 weeks of isocaloric high protein feeding, and that the elevation in AUC-leptin will predict the extent to which caloric intake decreases when subjects are switched from an isocaloric to an ad libitum high protein diet.
Specific Aim 1: To determine whether an isocaloric increase in dietary protein content from 15% to 30% causes a significant increase in AUC-leptin and AUC-insulin that is sustained for two weeks.
Specific Aim 2: To determine whether the increase in AUC-leptin on a 30% protein diet predicts a subsequent decrease in ad libitum caloric intake and weight loss.
- Conditions
- Dietary Exposure
- Being tested
- High protein diet
- Keywords
- protein
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High protein dietOther
Normal vs high protein dietary feeding
| Study group | Role | What they receive |
|---|---|---|
| High protein feeding | Experimental | Two isocaloric feeding phases of 2 weeks followed by an ad-libitum feeding phase of 3 months Receives: Other: High protein diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
24 hour levels of leptin after isocaloric and ad-libitum feeding phases
Change in leptin levels measured every 30 minutes while consuming diet-assigned meals
Measured: After each 2 week isocaloric feeding phase (x2) and a 3 month ad-lib feeding phase
24 hour levels of ghrelin after isocaloric and ad-libitum feeding phases
Change in ghrelin levels measured every 30 minutes while consuming diet-assigned meals
Measured: After each 2 week isocaloric feeding phase (x2) and a 3 month ad-lib feeding phase
Body weight
Change in body weight
Measured: Weekly during each 2 week isocaloric feeding phase (x2) and a 3 month ad-lib feeding phase
Secondary outcomes (2)
Appetite scores
Changes in self-reported visual analog scores (VAS) for hunger, fullness measured every 30 minutes while consuming diet-assigned meals
Measured: Daily during each 2 week isocaloric feeding phase (x2) and a 3 month ad-lib feeding phase
Lipid levels at each study visit
Changes in lipid levels at the end of the trial phases involving different diet-assigned meals
Measured: Daily during each 2 week isocaloric feeding phase (x2) and a 3 month ad-lib feeding phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2021
- Study start1 May 2002
- Primary completion31 Dec 2003
- Study completion31 Dec 2003
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 Dietary ExposureStudies of the same condition, open and under way.
- More trials run by Oregon Health and Science UniversityThe 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
- Sequential
- Model description
- Isocaloric feeding phase followed by ad-libitum feeding phase
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jonathan Purnell, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05002491
- Sponsor's protocol ID
- Protocol 695
- Acronym
- HiProLep
- Status last verified
- Aug 2021
- First submitted
- 20 Jul 2021
- Last updated
- 30 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Weigle DS, Breen PA, Matthys CC, Callahan HS, Meeuws KE, Burden VR, Purnell JQ. A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr. 2005 Jul;82(1):41-8. doi: 10.1093/ajcn.82.1.41.
PubMed 16002798Koren MS, Purnell JQ, Breen PA, Matthys CC, Callahan HS, Meeuws KE, Burden VR, Weigle DS. Changes in plasma amino Acid levels do not predict satiety and weight loss on diets with modified macronutrient composition. Ann Nutr Metab. 2007;51(2):182-7. doi: 10.1159/000103323. Epub 2007 May 30.
PubMed 17541265Kratz M, Weigle DS, Breen PA, Meeuws KE, Burden VR, Callahan HS, Matthys CC, Purnell JQ. Exchanging carbohydrate or protein for fat improves lipid-related cardiovascular risk profile in overweight men and women when consumed ad libitum. J Investig Med. 2010 Jun;58(5):711-9. doi: 10.231/JIM.0b013e3181da4d37.
PubMed 20305576Kremsdorf RA, Hoofnagle AN, Kratz M, Weigle DS, Callahan HS, Purnell JQ, Horgan AM, de Boer IH, Kestenbaum BR. Effects of a high-protein diet on regulation of phosphorus homeostasis. J Clin Endocrinol Metab. 2013 Mar;98(3):1207-13. doi: 10.1210/jc.2012-2910. Epub 2013 Feb 7.
PubMed 23393178Horgan AM, Palmbach GR, Jordan JM, Callahan HS, Meeuws KE, Weigle DS, Kratz M, Purnell JQ. Self-selected meal composition alters the relationship between same-day caloric intake and appetite scores in humans during a long-term ad-libitum feeding study. Eur J Nutr. 2023 Mar;62(2):1003-1009. doi: 10.1007/s00394-022-03040-5. Epub 2022 Nov 8.
PubMed 36346472
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Change in Leptin as a Predictor of Satiety With High Protein Feeding
- ClinicalTrials.gov ID
- NCT05002491
- Acronym / sponsor ID
- HiProLep / Protocol 695
- Conditions
- Dietary Exposure
- Keywords
- protein
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Study start
- 1 May 2002 (actual)
- Primary completion
- 31 Dec 2003 (actual)
- Study completion
- 31 Dec 2003 (actual)
- First posted
- 12 Aug 2021 (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.
Body weight can be affected by the content of fat and carbohydrate in the diet. On average, people will lose a modest (< 5 kg) amount of weight when switched from a high fat diet to a low fat, high carbohydrate diet. Determining mechanisms whereby changing the makeup of the diet can change one's body weight will be important in understanding why body weight in the US population is trending upward recently and what health care providers can recommend to reverse this trend. Previous studies have shown that increasing the carbohydrate and lowering the fat content in the diet leads to a change in the appearance of the hormone leptin in the blood over 24 hours. Leptin is an important signal from the fat cell to the brain that leads to a reduction in appetite and weight loss. A previous study found that after keeping people's weight stable, that the greater rise in leptin over the day on a low fat-high carbohydrate diet compared to a high fat diet predicted the reduction in calories they ate over a subsequent 12 weeks when their weight was allowed to freely fluctuate. Recent studies have also provided evidence that limiting fat and increasing the amount of protein in the diet also leads to modest weight loss. It is therefore proposed to test whether low fat, high protein diets also result a change in leptin secretion, and if this change predicts a reduction in appetite when they are allowed to eat freely.
Detailed description
The role of leptin in regulating body fat mass in humans is incompletely understood. Although complete loss of leptin signaling results in morbid obesity, there is an inconsistent association between more subtle changes in leptin levels and changes in body composition. Administration of recombinant leptin to human volunteers also results in a variable loss of fat mass. Therapeutic high carbohydrate diets generally lead to decreased caloric intake and weight loss compared with high fat diets. The mechanism of this decrease in appetite is, however, unknown. In preliminary data, the invesigators have shown that compared to high fat feeding, isocaloric high carbohydrate feeding over 2 weeks leads to increased leptin excursion during 24 hours. In addition, this change in leptin signaling predicts subsequent reduction in daily caloric intake with ad-lib high carbohydrate feeding. It has recently been reported that an increase in dietary protein also leads to modest spontaneous weight loss in ad-lib feeding subjects. The current proposal is to therefore determine whether prolonged high protein feeding leads to a sustained increase in the integrated daily leptin level and whether this increase predicts a subsequent decrease in caloric intake in human volunteers. Eligible subjects will consume a control protein diet (15%, low protein) followed by a high protein diet (30% protein) for 2 weeks each while maintaining weight stability. At the end of each 2-week feeding phase, subjects will be admitted to the inpatient GCRC for frequent sampling for insulin and leptin levels over 24 hours. Immediately following the second CRC inpatient visit, subjects will continue to consume the high protein diet ad-libitum for another 12 weeks, during which time they will be followed for changes in their caloric intake and body weight. Because of limitations in metabolic kitchen resources, if this study were to be conducted solely at OHSU, it would require recruitment and study of two groups of subjects over sequential time periods. This results in delay of acquisition of data, completion of the study, and the potential introduction of seasonal variation as a study confounder. Therefore, a two-site study is proposed utilizing the metabolic kitchen resources of OHSU and the University of Washington GCRC's jointly. Instead of two groups of subjects being recruited and studied sequentially at one site, subjects will be recruited at both sites and studied in parallel, thus allowing the completion of the protocol in half the usual amount of time and without additional study confounders.
It is hypothesized that switching human volunteers from a 15% protein diet to an isocaloric high (30%) protein diet will cause a significant increase in the area under the diurnal plasma leptin versus time curve (AUC-leptin) and the insulin versus time curve (AUC-insulin), that these increases will be sustained over 2 weeks of isocaloric high protein feeding, and that the elevation in AUC-leptin will predict the extent to which caloric intake decreases when subjects are switched from an isocaloric to an ad libitum high protein diet.
Specific Aim 1: To determine whether an isocaloric increase in dietary protein content from 15% to 30% causes a significant increase in AUC-leptin and AUC-insulin that is sustained for two weeks.
Specific Aim 2: To determine whether the increase in AUC-leptin on a 30% protein diet predicts a subsequent decrease in ad libitum caloric intake and weight loss.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Isocaloric feeding phase followed by ad-libitum feeding phase
| Arm | Type | Receives |
|---|---|---|
| High protein feeding | Experimental | Other: High protein dietTwo isocaloric feeding phases of 2 weeks followed by an ad-libitum feeding phase of 3 months |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Ability to provide informed written consent
- Age between 18 and 65 years
- Willingness to consume only food prepared by the CRC for 6 weeks
- Body mass index between 22 and 28 kg/m2
- Weight stable to within 2 kg for 3 months preceding study, and at lifetime maximal weight
Key exclusion criteria (9 listed)
- Diabetes mellitus
- Renal disease
- Other chronic medical or psychiatric illness
- Pregnancy or female subject unwilling to use contraception
- Use of tobacco products
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 dietNormal vs high protein dietary feeding | Other | High protein feeding |
Primary outcome
24 hour levels of leptin after isocaloric and ad-libitum feeding phases
Time frame: After each 2 week isocaloric feeding phase (x2) and a 3 month ad-lib feeding phase
Change in leptin levels measured every 30 minutes while consuming diet-assigned meals
24 hour levels of ghrelin after isocaloric and ad-libitum feeding phases
Time frame: After each 2 week isocaloric feeding phase (x2) and a 3 month ad-lib feeding phase
Change in ghrelin levels measured every 30 minutes while consuming diet-assigned meals
Body weight
Time frame: Weekly during each 2 week isocaloric feeding phase (x2) and a 3 month ad-lib feeding phase
Change in body weight
2 secondary outcomes
Appetite scores
Time frame: Daily during each 2 week isocaloric feeding phase (x2) and a 3 month ad-lib feeding phase
Lipid levels at each study visit
Time frame: Daily during each 2 week isocaloric feeding phase (x2) and a 3 month ad-lib feeding phase
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 30 Aug 2021.
- Background: PubMed 16002798Weigle DS, Breen PA, Matthys CC, Callahan HS, Meeuws KE, Burden VR, Purnell JQ. A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr. 2005 Jul;82(1):41-8. doi: 10.1093/ajcn.82.1.41.
- Background: PubMed 17541265Koren MS, Purnell JQ, Breen PA, Matthys CC, Callahan HS, Meeuws KE, Burden VR, Weigle DS. Changes in plasma amino Acid levels do not predict satiety and weight loss on diets with modified macronutrient composition. Ann Nutr Metab. 2007;51(2):182-7. doi: 10.1159/000103323. Epub 2007 May 30.
- Background: PubMed 20305576Kratz M, Weigle DS, Breen PA, Meeuws KE, Burden VR, Callahan HS, Matthys CC, Purnell JQ. Exchanging carbohydrate or protein for fat improves lipid-related cardiovascular risk profile in overweight men and women when consumed ad libitum. J Investig Med. 2010 Jun;58(5):711-9. doi: 10.231/JIM.0b013e3181da4d37.
- Background: PubMed 23393178Kremsdorf RA, Hoofnagle AN, Kratz M, Weigle DS, Callahan HS, Purnell JQ, Horgan AM, de Boer IH, Kestenbaum BR. Effects of a high-protein diet on regulation of phosphorus homeostasis. J Clin Endocrinol Metab. 2013 Mar;98(3):1207-13. doi: 10.1210/jc.2012-2910. Epub 2013 Feb 7.
- Derived from this study: PubMed 36346472Horgan AM, Palmbach GR, Jordan JM, Callahan HS, Meeuws KE, Weigle DS, Kratz M, Purnell JQ. Self-selected meal composition alters the relationship between same-day caloric intake and appetite scores in humans during a long-term ad-libitum feeding study. Eur J Nutr. 2023 Mar;62(2):1003-1009. doi: 10.1007/s00394-022-03040-5. Epub 2022 Nov 8.
- 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.
Questions about this trial
What is this clinical trial studying?
A study testing High protein diet in people with Dietary Exposure, run by Oregon Health and Science University.
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 9 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 30 Aug 2021. 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?
24 hour levels of leptin after isocaloric and ad-libitum feeding phases (time frame: After each 2 week isocaloric feeding phase (x2) and a 3 month ad-lib feeding phase). The study lists 3 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 NCT05002491, 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 30 Aug 2021.