Insulin ResistanceNCT02193295
Reversal of Lipid-Induced Insulin Resistance
A study testing Caloric Restriction in people with Insulin Resistance and NAFLD, run by Yale University at 2 sites in United States.
Trial summary
The purpose of this study is to examine whether weight reduction decreases intramyocellular (IMCL) and hepatic lipid content, and improves insulin sensitivity of muscle and fat tissue in people who are insulin resistant and have a family history of type 2 diabetes. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance, NAFLD
- What is being tested?
- Caloric Restriction
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2002to Dec 2034
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy, sedentary, non-smoking and not taking any medications other than birth control pills.
- Hematocrit >35%
- Subjects will have no systemic or organ disease including diabetes.
- Subjects will have no history eating disorders.
- Women must be using a form of birth control (sexual abstinence, birth control pills, Norplant, IUD or condoms) and will be studied between day 0 and 7 of their menstrual cycle.
- Those who are taking birth control pills or have had a hysterectomy may be studied at any time.
- Physical activity will be assessed using a standard questionnaire with an activity index cut off at 2.3.
Who cannot join
- Any subject, who does not fit the inclusion criteria. Including history of eating disorders, any systemic and organ disease including diabetes.
- Lactose intolerance Any blood count, clotting abnormalities HYpertriglyceridemeia (TG over 100 mg/dL)
- Hematocrit <35%.
- Women of childbearing potential, who are not using contraception (as mentioned above) or who are not abstinent.
- Subjects who have a regular exercise regimen will not be enrolled.
- Metal implants and/or body piercing, which cannot be removed before the MR studies.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Enrolling by invitation
Magnetic Resonance Research Center (MRRC)
New Haven, Connecticut, 06511
- Recruiting
Yale Center for Clinical Investigation HRU
New Haven, Connecticut, 06520
Kitt Petersen, MD, 203-688-4106
Kitt Petersen, MD
About this study
The purpose of this study is to examine whether weight reduction decreases intramyocellular (IMCL) and hepatic lipid content, and improves insulin sensitivity of muscle and fat tissue in people who are insulin resistant and have a family history of type 2 diabetes.
Hepatic mitochondrial oxidation will be assesses using a 3 hour triple tracer study (D7 glucose, 3-13C lactate and 13C4 beta-hydroxybutyrate).
Read the detailed description
In this study, we will examine whether a small weight loss in lean, insulin-resistant offspring of type 2 diabetic patients will improve insulin resistance. The control group will consist of subjects matched for gender, age and body weight with no family history of diabetes. Before and after weight loss, rates of basal and insulin stimulated whole body glucose metabolism will be measured using [6,6-2H] glucose during a 3 hour basal period and a 4 hour euglycemic hyperinsulinemic (20 mU/m2-min) clamp. Rates of whole body lipolysis will be determined using [2H5] glycerol, localized rates of lipolysis will be measured using the microdialysis technique and muscle PI 3-kinase activity will be assessed in muscle biopsies. FFA metabolites (fatty acyl CoA, ceramides, diacylglycerol) will be measured in fat tissue collected from the abdominal subcutaneous fat cell depot. Body composition will be determined with bioelectrical impedance and whole body MRI; IMCL will be measured with MRS. Before and after weight loss, insulin secretion will be measured with the hyperglycemic clamp (as described under Day 2 Hyperglycemic Clamp).
Hepatic mitochondrial fat oxidation will be assessed in a separate study at baseline. Participants will be admitted to the Yale HRU at 7 AM after an overnight fast. An IV line will be placed in antecubital vein for tracer infusions and a retrograde IV line will be placed in a hand vein for blood collections. The hand will be warmed in a 'hot box' 37°C to approximate collection of 'arterial' blood samples. After collection of a baseline blood samples, infusions of 13C lactate (0.9 mM, 99% 13C, infusion rate: 8.7 micromol/(Kg-min)), D7glucose (25 mg/mL, 99% 13C, infusion rate: 0.84 mg/(m2-min)) and 13C-BHOB (2 mg/mL, 99%rate: 0.01 mg/(Kg-min)) will be started and continued for 180 minutes. During the final 20 minutes of this infusion period blood samples will be collected from the retrograde IV line. The infusion will then be discontinued the IV lines removed, and the participants will be served breakfast/lunch and discharged to home.
- Conditions
- Insulin Resistance, NAFLD
- Being tested
- Caloric Restriction
- Keywords
- Weight Reduction, Caloric Restriction, Euglycemic Hyperinsulinemic Clamp, Magnetic Resonance Spectroscopy, PINTA
- Medical subject headings
- Insulin Resistance, Non-alcoholic Fatty Liver Disease, Weight Loss, Pinta
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caloric RestrictionBehavioural
Also called Dietary intervention to reduce lipid content in liver and muscle with minimal overall weight loss.
Dietary intervention to reduce lipid content in liver and muscle with minimal overall weight loss. Weekly visits for measurements of body weight, body composition, blood glucose and MRS measurements of liver and muscle lipid.
| Study group | Role | What they receive |
|---|---|---|
| Lifestyle Intervention | Experimental | Caloric Restriction to reverse lipid-induced insulin resistance. Receives: Behavioral: Caloric Restriction |
| Baseline Assessment of Hepatic Mitochondrial Fat Oxidation | Experimental | Tracer study to assess hepatic mitochondrial fat oxidation (PINTA). Receives: Behavioral: Caloric Restriction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvements in insulin sensitivity
Insulin sensitivity will be assessed using the insulin/glucose clamp, liver and muscle fat will be measured using 1H magnetic resonance spectroscopy (MRS) and both results from the clamp and MRS compared to baseline values before the weight reduction intervention.
Measured: up to 6 months intervention to examine whether insulin sensitivity has improved significantly after the moderate weight reduction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2014 (estimated)
- Study startOct 2002
- Primary completionOct 2034 (estimated)
- Study completionDec 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by Yale 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kitt Petersen, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02193295
- Sponsor's protocol ID
- 02029020997_a
- Other IDs
- R01DK135645
- Status last verified
- Jun 2026
- First submitted
- 25 Jun 2014
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Unidentified data will be provided to other investigators upon reasonable request after any publication of final data.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reversal of Lipid-Induced Insulin Resistance
- ClinicalTrials.gov ID
- NCT02193295
- Acronym / sponsor ID
- 02029020997_a
- Conditions
- Insulin Resistance, NAFLD
- Keywords
- Weight Reduction, Caloric Restriction, Euglycemic Hyperinsulinemic Clamp, Magnetic Resonance Spectroscopy, PINTA
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Oct 2002 (actual)
- Primary completion
- Oct 2034 (estimated)
- Study completion
- Dec 2034 (estimated)
- First posted
- 17 Jul 2014 (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 purpose of this study is to examine whether weight reduction decreases intramyocellular (IMCL) and hepatic lipid content, and improves insulin sensitivity of muscle and fat tissue in people who are insulin resistant and have a family history of type 2 diabetes.
Hepatic mitochondrial oxidation will be assesses using a 3 hour triple tracer study (D7 glucose, 3-13C lactate and 13C4 beta-hydroxybutyrate).
Detailed description
In this study, we will examine whether a small weight loss in lean, insulin-resistant offspring of type 2 diabetic patients will improve insulin resistance. The control group will consist of subjects matched for gender, age and body weight with no family history of diabetes. Before and after weight loss, rates of basal and insulin stimulated whole body glucose metabolism will be measured using [6,6-2H] glucose during a 3 hour basal period and a 4 hour euglycemic hyperinsulinemic (20 mU/m2-min) clamp. Rates of whole body lipolysis will be determined using [2H5] glycerol, localized rates of lipolysis will be measured using the microdialysis technique and muscle PI 3-kinase activity will be assessed in muscle biopsies. FFA metabolites (fatty acyl CoA, ceramides, diacylglycerol) will be measured in fat tissue collected from the abdominal subcutaneous fat cell depot. Body composition will be determined with bioelectrical impedance and whole body MRI; IMCL will be measured with MRS. Before and after weight loss, insulin secretion will be measured with the hyperglycemic clamp (as described under Day 2 Hyperglycemic Clamp).
Hepatic mitochondrial fat oxidation will be assessed in a separate study at baseline. Participants will be admitted to the Yale HRU at 7 AM after an overnight fast. An IV line will be placed in antecubital vein for tracer infusions and a retrograde IV line will be placed in a hand vein for blood collections. The hand will be warmed in a 'hot box' 37°C to approximate collection of 'arterial' blood samples. After collection of a baseline blood samples, infusions of 13C lactate (0.9 mM, 99% 13C, infusion rate: 8.7 micromol/(Kg-min)), D7glucose (25 mg/mL, 99% 13C, infusion rate: 0.84 mg/(m2-min)) and 13C-BHOB (2 mg/mL, 99%rate: 0.01 mg/(Kg-min)) will be started and continued for 180 minutes. During the final 20 minutes of this infusion period blood samples will be collected from the retrograde IV line. The infusion will then be discontinued the IV lines removed, and the participants will be served breakfast/lunch and discharged to home.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lifestyle Intervention | Experimental | Behavioral: Caloric RestrictionCaloric Restriction to reverse lipid-induced insulin resistance. |
| Baseline Assessment of Hepatic Mitochondrial Fat Oxidation | Experimental | Behavioral: Caloric RestrictionTracer study to assess hepatic mitochondrial fat oxidation (PINTA). |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Healthy, sedentary, non-smoking and not taking any medications other than birth control pills.
- Hematocrit >35%
- Subjects will have no systemic or organ disease including diabetes.
- Subjects will have no history eating disorders.
- Women must be using a form of birth control (sexual abstinence, birth control pills, Norplant, IUD or condoms) and will be studied between day 0 and 7 of their menstrual cycle.
Key exclusion criteria (6 listed)
- Any subject, who does not fit the inclusion criteria. Including history of eating disorders, any systemic and organ disease including diabetes.
- Lactose intolerance Any blood count, clotting abnormalities HYpertriglyceridemeia (TG over 100 mg/dL)
- Hematocrit <35%.
- Women of childbearing potential, who are not using contraception (as mentioned above) or who are not abstinent.
- Subjects who have a regular exercise regimen will not be enrolled.
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 |
|---|---|---|
| Caloric RestrictionAlso: Dietary intervention to reduce lipid content in liver and muscle with minimal overall weight loss.Dietary intervention to reduce lipid content in liver and muscle with minimal overall weight loss. Weekly visits for measurements of body weight, body composition, blood glucose and MRS measurements of liver and muscle lipid. | Behavioural | Baseline Assessment of Hepatic Mitochondrial Fat Oxidation, Lifestyle Intervention |
Primary outcome
Improvements in insulin sensitivity
Time frame: up to 6 months intervention to examine whether insulin sensitivity has improved significantly after the moderate weight reduction
Insulin sensitivity will be assessed using the insulin/glucose clamp, liver and muscle fat will be measured using 1H magnetic resonance spectroscopy (MRS) and both results from the clamp and MRS compared to baseline values before the weight reduction intervention.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Individual participant dataSharing planned: No. Unidentified data will be provided to other investigators upon reasonable request after any publication of final data.
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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.
Kitt Petersen, MD principal investigator
Yale University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Caloric Restriction in people with Insulin Resistance and NAFLD, run by Yale University at 2 sites 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 7 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kitt Petersen, MD (203-785-5447, kitt.petersen@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvements in insulin sensitivity (time frame: up to 6 months intervention to examine whether insulin sensitivity has improved significantly after the moderate weight reduction). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Jun 2026.