ObesityNCT01520454
Effect of Increased Free Fatty Acids on Leptin Function
A study testing Saline, Intralipid and Water in people with Obesity and Leptin Resistance, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
Obese people have elevated levels of the hormone leptin. Despite this, they seem to be resistant to the effects of this hormone, which usually regulates appetite and energy expenditure. This is similar to what happens with insulin levels in the obese. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Leptin Resistance
- What is being tested?
- Saline, Intralipid and Water
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to Dec 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age 18-65
Who cannot join
- Subjects with a history of any illness, other than obesity, that may affect insulin sensitivity (anemia, infectious diseases, renal or hepatic failure, uncontrolled hypertension, cancer, lymphoma, chronic inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis, states of cortisol or growth hormone excess, alcoholism or drug abuse, and eating disorders).
- History of diabetes mellitus.
- Subjects taking any medications that are known to influence glucose metabolism such as glucocorticoids will also be excluded. We will screen for these conditions by means of a detailed history and review of systems and physical examination (see below).
- Subjects taking any medications known to affect lipids such as statins will also be excluded. We will screen for these similar to above.
- Cholesterol greater or equal to 250 mg/dL and/or triglyceride levels greater than 500 mg/dL at the time of screening, as determined by laboratory testing.
- Subjects who have a known history of anaphylaxis or anaphylactoid-like reactions or who have a known hypersensitivity to anesthetic agents such as Lidocaine or Marcaine will be excluded from the study.
Show all 13Show fewer
- Hypersensitivity to fat emulsion or any component of the formulation; severe egg or legume (soybean) allergies; pathologic hyperlipidemia, lipoid nephrosis, acute pancreatitis associated with hyperlipemia.
- Hypersensitivity to heparin or any component of the formulation
- Severe thrombocytopenia, uncontrolled active bleeding, disseminated intravascular coagulation (DIC); suspected intracranial hemorrhage.
- Subjects with a history of bleeding dyscrasia, poor wound healing or any medical condition precluding supine position will be excluded from the study.
- Unable to follow study protocol or any condition that in the opinion of the investigator makes the subject unsuitable for the study.
- Pregnancy
- Prior history of gastrectomy, gastric bypass surgery, or other weight loss surgery.
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: Differential Effects of Oral and Intravenous Lipid Administration on Leptin Signaling
Obese people have elevated levels of the hormone leptin. Despite this, they seem to be resistant to the effects of this hormone, which usually regulates appetite and energy expenditure. This is similar to what happens with insulin levels in the obese. Furthermore, the way lipid ingestion versus lipid infusion may impact novel molecules secreted by tissues commonly affected in insulin resistant states such as liver and muscle have not yet been studied.
The aim of the present study is to investigate the effect of oral vs. different doses of IV lipid administration on molecular parameters related to glucose and energy homeostasis using a randomized, placebo-controlled design.
Additionally, we will examine how increased free fatty acids (FFAs) my impact intracellular leptin signaling such as the STAT3 pathway.
Read the detailed description
We propose to test our hypotheses by conducting a non-blinded, interventional study evaluating the effects of acute leptin administration on intracellular leptin signaling pathways after a 6 hour infusion period comparing an oral high fat meal, high fat lipid infusion, low fat lipid infusion, or placebo infusion (saline)iv lipid infusion, placebo (saline) and oral high fat meal. After a screening visit, study participation involves 1 meal pick-up visit, 1 overnight visit, and one 1 follow-up visit. Subjects will be randomized to one of 4 groups: an oral high fat meal, fat emulsion 20% infusion , fat emulsion 10% infusion, and a placebo (saline) infusion infusion and an oral high fat meal.
We plan to screen 100 male and postmenopausal female subjects, with BMI greater than 18 kg/m2, to consent 60 in order to have 32-48 evaluable subjects, 8-12 subjects per group, completing all parts of the study.
The primary study outcome to be evaluated will be the changes in serum concentrations of glucose, hormones influencing metabolism such as insulin, fat-cell-secreted proteins such as leptin, molecules involved in metabolism such as free fatty acids (FFAs), and markers of inflammation such as interleukin (IL)-2 and interferon (IFN)-gamma.
The secondary outcome will be to examine the impacts of increased FFAs on intracellular leptin signaling by phosphorylation of STAT3.
- Conditions
- Obesity, Leptin Resistance
- Being tested
- Saline, Intralipid, Water, oral fat, Heparin
- Keywords
- Leptin resistance, Free fatty acids, Lipotoxicity
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalineDrug
IV saline at 0.83 mL/kg/hr for six hours
IntralipidDrug
Also called intravenous lipids
Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours
WaterDietary supplement
Water by mouth
oral fatDietary supplement
Also called soybean oil
Soybean oil by mouth at 1.25 g/kg x 2 doses
HeparinDrug
Also called anti coated
Heparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | IV saline with heparin, oral water Receives: Drug: Saline; Dietary Supplement: Water; Drug: Heparin |
| High dose fat solution | Experimental | Intralipid at high dose, with heparin and PO water Receives: Drug: Intralipid; Dietary Supplement: Water; Drug: Heparin |
| Low dose fat solution | Experimental | Low dose IV Intralipid with heparin and PO water Receives: Drug: Intralipid; Dietary Supplement: Water; Drug: Heparin |
| Oral fat | Experimental | Oral fat load with IV saline Receives: Drug: Saline; Dietary Supplement: Water; Dietary Supplement: oral fat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Circulating Glucagon-like Peptide-1 (GLP-1) Levels
The GLP-1 area under the curve (AUC) was calculated from baseline to six hours
Measured: Baseline to 6 hours
Change in Circulating Gastric Inhibitory Polypeptide (GIP) Levels
The GIP AUC fwas calculated from baseline to six hours
Measured: Baseline to 6 hours
Change in Circulating Ghrelin Levels
The Ghrelin AUC was calculated from baseline to six hours
Measured: Baseline to 6 hours
Change in Circulating Peptide Tyrosine Tyrosine (PYY) Levels
The PYY AUC was calculated from baseline to six hours
Measured: Baseline to 6 hours
Secondary outcomes (5)
Change in Circulating Glucose Levels
The Glucose AUC was calculated from baseline to six hours
Measured: Baseline to 6 hours
Change in Circulating Insulin Levels
The Insulin AUC was calculated from baseline to six hours
Measured: Baseline to 6 hours
Change in Circulating Leptin Levels
The Leptin AUC was calculated from baseline to six hours
Measured: Baseline to 6 hours
Change in Circulating Adiponectin Levels
The Adiponectin AUC was calculated from baseline to six hours
Measured: Baseline to 6 hours
Phosphorylation of STAT3 Pathways Downstream of Leptin After Lipid Administration
Intracellular signaling mechanisms downstream of leptin (particularly the STAT3 pathway) in response to lipid administration as represented by phosphorylation (pSTAT3).
Measured: Baseline to 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2012 (estimated)
- Study startNov 2011
- Primary completionDec 2013
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christos Mantzoros, Beth Israel Deaconess Medical Center
- Investigators
- Christos S Mantzoros, MD, DSc, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01520454
- Sponsor's protocol ID
- 2009P000370
- Status last verified
- May 2018
- First submitted
- 4 Jan 2012
- Last updated
- 11 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Perakakis N, Kokkinos A, Angelidi AM, Tsilingiris D, Gavrieli A, Yannakoulia M, Tentolouris N, Mantzoros CS. Circulating levels of five proglucagon-derived peptides in response to intravenous or oral glucose or lipids and to a mixed-meal in subjects with normal weight, overweight, and obesity. Clin Nutr. 2022 Sep;41(9):1969-1976. doi: 10.1016/j.clnu.2022.07.001. Epub 2022 Jul 19.
PubMed 35961260
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Differential Effects of Oral and Intravenous Lipid Administration on Leptin Signaling
- ClinicalTrials.gov ID
- NCT01520454
- Acronym / sponsor ID
- 2009P000370
- Conditions
- Obesity, Leptin Resistance
- Keywords
- Leptin resistance, Free fatty acids, Lipotoxicity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 30 Jan 2012 (estimated)
- Results
- Posted 26 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Obese people have elevated levels of the hormone leptin. Despite this, they seem to be resistant to the effects of this hormone, which usually regulates appetite and energy expenditure. This is similar to what happens with insulin levels in the obese. Furthermore, the way lipid ingestion versus lipid infusion may impact novel molecules secreted by tissues commonly affected in insulin resistant states such as liver and muscle have not yet been studied.
The aim of the present study is to investigate the effect of oral vs. different doses of IV lipid administration on molecular parameters related to glucose and energy homeostasis using a randomized, placebo-controlled design.
Additionally, we will examine how increased free fatty acids (FFAs) my impact intracellular leptin signaling such as the STAT3 pathway.
Detailed description
We propose to test our hypotheses by conducting a non-blinded, interventional study evaluating the effects of acute leptin administration on intracellular leptin signaling pathways after a 6 hour infusion period comparing an oral high fat meal, high fat lipid infusion, low fat lipid infusion, or placebo infusion (saline)iv lipid infusion, placebo (saline) and oral high fat meal. After a screening visit, study participation involves 1 meal pick-up visit, 1 overnight visit, and one 1 follow-up visit. Subjects will be randomized to one of 4 groups: an oral high fat meal, fat emulsion 20% infusion , fat emulsion 10% infusion, and a placebo (saline) infusion infusion and an oral high fat meal.
We plan to screen 100 male and postmenopausal female subjects, with BMI greater than 18 kg/m2, to consent 60 in order to have 32-48 evaluable subjects, 8-12 subjects per group, completing all parts of the study.
The primary study outcome to be evaluated will be the changes in serum concentrations of glucose, hormones influencing metabolism such as insulin, fat-cell-secreted proteins such as leptin, molecules involved in metabolism such as free fatty acids (FFAs), and markers of inflammation such as interleukin (IL)-2 and interferon (IFN)-gamma.
The secondary outcome will be to examine the impacts of increased FFAs on intracellular leptin signaling by phosphorylation of STAT3.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Saline, Dietary Supplement: Water, Drug: HeparinIV saline with heparin, oral water |
| High dose fat solution | Experimental | Drug: Intralipid, Dietary Supplement: Water, Drug: HeparinIntralipid at high dose, with heparin and PO water |
| Low dose fat solution | Experimental | Drug: Intralipid, Dietary Supplement: Water, Drug: HeparinLow dose IV Intralipid with heparin and PO water |
| Oral fat | Experimental | Drug: Saline, Dietary Supplement: Water, Dietary Supplement: oral fatOral fat load with IV saline |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Age 18-65
Key exclusion criteria (13 listed)
- Subjects with a history of any illness, other than obesity, that may affect insulin sensitivity (anemia, infectious diseases, renal or hepatic failure, uncontrolled hypertension, cancer, lymphoma, chronic inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis, states of cortisol or growth hormone excess, alcoholism or drug abuse, and eating disorders).
- History of diabetes mellitus.
- Subjects taking any medications that are known to influence glucose metabolism such as glucocorticoids will also be excluded. We will screen for these conditions by means of a detailed history and review of systems and physical examination (see below).
- Subjects taking any medications known to affect lipids such as statins will also be excluded. We will screen for these similar to above.
- Cholesterol greater or equal to 250 mg/dL and/or triglyceride levels greater than 500 mg/dL at the time of screening, as determined by laboratory testing.
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 |
|---|---|---|
| SalineIV saline at 0.83 mL/kg/hr for six hours | Drug | Oral fat, Placebo |
| IntralipidAlso: intravenous lipidsIntralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours | Drug | High dose fat solution, Low dose fat solution |
| WaterWater by mouth | Dietary supplement | High dose fat solution, Low dose fat solution, Oral fat, Placebo |
| oral fatAlso: soybean oilSoybean oil by mouth at 1.25 g/kg x 2 doses | Dietary supplement | Oral fat |
| HeparinAlso: anti coatedHeparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours | Drug | High dose fat solution, Low dose fat solution, Placebo |
Primary outcome
Change in Circulating Glucagon-like Peptide-1 (GLP-1) Levels
Time frame: Baseline to 6 hours
The GLP-1 area under the curve (AUC) was calculated from baseline to six hours
Change in Circulating Gastric Inhibitory Polypeptide (GIP) Levels
Time frame: Baseline to 6 hours
The GIP AUC fwas calculated from baseline to six hours
Change in Circulating Ghrelin Levels
Time frame: Baseline to 6 hours
The Ghrelin AUC was calculated from baseline to six hours
Change in Circulating Peptide Tyrosine Tyrosine (PYY) Levels
Time frame: Baseline to 6 hours
The PYY AUC was calculated from baseline to six hours
5 secondary outcomes
Change in Circulating Glucose Levels
Time frame: Baseline to 6 hours
Change in Circulating Insulin Levels
Time frame: Baseline to 6 hours
Change in Circulating Leptin Levels
Time frame: Baseline to 6 hours
Change in Circulating Adiponectin Levels
Time frame: Baseline to 6 hours
Phosphorylation of STAT3 Pathways Downstream of Leptin After Lipid Administration
Time frame: Baseline to 6 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35961260Perakakis N, Kokkinos A, Angelidi AM, Tsilingiris D, Gavrieli A, Yannakoulia M, Tentolouris N, Mantzoros CS. Circulating levels of five proglucagon-derived peptides in response to intravenous or oral glucose or lipids and to a mixed-meal in subjects with normal weight, overweight, and obesity. Clin Nutr. 2022 Sep;41(9):1969-1976. doi: 10.1016/j.clnu.2022.07.001. Epub 2022 Jul 19.
- Mantzoros Lab Home PageLink provided by the sponsor.
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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.
Christos S Mantzoros, MD, DSc principal investigator
Beth Israel Deaconess Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Saline, Intralipid and Water in people with Obesity and Leptin Resistance, run by Beth Israel Deaconess Medical Center at 1 site in United States.
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 1 inclusion and 13 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 11 May 2018. 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 States. 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?
Yes. Results are posted in the registry (first posted 26 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Circulating Glucagon-like Peptide-1 (GLP-1) Levels (time frame: Baseline to 6 hours). The study lists 4 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 NCT01520454, 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 11 May 2018; AzTrials last refreshed its copy on 30 Oct 2026.