Other Fatty Acid Oxidation DisordersNCT02348190
Fat Induced Insulin Resistance and Atherosclerosis
A study testing Lipid/heparin in people with Other Fatty Acid Oxidation Disorders and Diabetes Mellitus, run by Temple University at 1 site in United States.
Trial summary
The overall objective of the current proposal is to strengthen the putative link between FFA induced insulin resistance and atherosclerotic vascular disease (ASVD). To this end, the investigators will test the following hypotheses: 1) that FFA induced activation of protein kinase C βII (PKC β II) and δ and other… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Other Fatty Acid Oxidation Disorders, Diabetes Mellitus, Insulin Resistance
- What is being tested?
- Lipid/heparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2003to Jun 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The investigators plan to study 32 healthy normal subjects.
- These volunteers will be male and female, between the ages of 30 and 75 years and of all races.
- None of these volunteers will have a family history of diabetes or any other endocrine disorder and none will be taking any medications.
Who cannot join
- Patients with chronic health problems including cardiovascular, pulmonary, hematologic (*Hb< 9 g/dl), renal (serum creatinine > 1.8 mg/dl), hepatic disease, AIDS or other chronic infectious disease will be excluded.
- Pregnant women will be excluded. Non-pregnant women will be studied during the follicular phase of their menstrual cycle. If needed, a pregnancy test will be performed to exclude pregnancy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Temple University Hospital
Philadelphia, Pennsylvania, 19140
About this study
The overall objective of the current proposal is to strengthen the putative link between FFA induced insulin resistance and atherosclerotic vascular disease (ASVD). To this end, the investigators will test the following hypotheses: 1) that FFA induced activation of protein kinase C βII (PKC β II) and δ and other serine kinases such as IκB kinase (IKK) in human muscle is associated with a decrease in insulin stimulated tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and of IRS-1 associated phosphatidylinositol 3 (PI3) kinase; 2) that these changes precede the development of insulin resistance; 3) that the decrease in IκB-α results in activation of nuclear factor κB (NFκB) and the expression of adhesion molecules and cytokines; 4) that PKC and IKK are involved in producing insulin resistance and activation of the IκB/ NFκB pathway and lastly 5) that the same mechanisms operative in healthy volunteers are also operative in patients with T2DM.The investigators will test these hypotheses in normal (current) and diabetic volunteers (previously completed) . Euglycemic-hyperinsulinemic clamps will be performed with and without co-infusion of lipid plus heparin (to raise FFAs) and by obtaining serial muscle and fat biopsies and blood samples will be obtained for measurement of substrates, hormones, enzymes and metabolites.
Read the detailed description
All subjects will be admitted to the GCRC in the afternoon before the tests (Day 1) and will undergo a thorough physical examination. Routine admission lab tests (including a 2-h 75g OGTT) and body composition measurements will be obtained. A standardized dinner will be served at ~ 6PM. The next (Day 2) after an overnight fast, IV lines will be placed (arms will be wrapped with a heating blanket and kept at 70ºF to arterialize venous blood).
The following studies will be performed.
Thirty-two healthy volunteers will undergo euglycemic - hyperinsulinemic clamping without radioactive isotopes and with (n=16) and without (n=16) lipid/heparin co-infusion for 8 hours.
Serial (at 0, 1, 2 and 4 h) muscle and fat biopsies and serial blood samples (q' 1 h) will be obtained. The following measurements will be obtained in muscle biopsies and T-cell extracts: PKC-βI and II and PKC-δ, IKK, IκB-α, NFκB, IRS-1 tyrosine phosphorylation, IRS-1 associated PI3- kinase, ICAM, VCAM and e-selectin mRNAs.
- Being tested
- Lipid/heparin
- Medical subject headings
- Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lipid/heparinOther
32 healthy volunteers will undergo euglycemic - hyperinsulinemic clamping without radioactive isotopes and with (n=16) and without (n=16) lipid/heparin co-infusion for 8 hours.
Serial (at 0, 1, 2 and 4 h) muscle and fat biopsies and serial blood samples (q' 1 h) will be obtained. The following measurements will be obtained in muscle biopsies and T-cell extracts: PKC-βI and II and PKC-δ, IKK, IκB-α, NFκB, IRS-1 tyrosine phosphorylation, IRS-1 associated PI3- kinase, ICAM, VCAM and e-selectin mRNAs.
| Study group | Role | What they receive |
|---|---|---|
| Lipid/heparin | Active comparator | 16 healthy volunteers will undergo euglycemic - hyperinsulinemic clamping without radioactive isotopes and with (n=16) lipid/heparin co-infusion for 8 hours. Receives: Other: Lipid/heparin |
| Control | Placebo comparator | 16 healthy volunteers will undergo euglycemic - hyperinsulinemic clamping without radioactive isotopes and without (n=16) lipid/heparin co-infusion for 8 hours. Receives: Other: Lipid/heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
protein kinase C enzyme activity in tissue samples
The following measurements will be obtained in muscle biopsies: PKC-βI and II and PKC-δ, IKK, IκB-α, NFκB, IRS-1 tyrosine phosphorylation, IRS-1 associated PI3- kinase, ICAM, VCAM and e-selectin mRNAs.
Measured: baseline, 1 hour, 2 hour, 4 hours
Secondary outcomes (3)
Insulin sensitivity
Glucose infusion rates during the 8 hour euglycemic-hyperinsulemic clamp will be calculated.
Measured: 0, 1, 2, 3, 4, 5, 6, 7, 8 hours
Free fatty acids
Free fatty acid levels will be measured by standard methods in the investigator's laboratory
Measured: 0, 1 2, 3, 4, 5, 6, 7 ,8 hours
protein kinase C enzyme activity in T cells
T cell extracts will be used to assay PKC, IKK, IκB-α, NFκB and VCAM, ICAM and e-selectin mRNA.
Measured: 0, 1, 2, 3, 4, 5, 6, 7, 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2015 (estimated)
- Study startJun 2003
- Primary completionDec 2014
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Other Fatty Acid Oxidation DisordersStudies 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
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Temple University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guenther Boden, MD, Principal investigator, Temple University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02348190
- Sponsor's protocol ID
- 4148
- Status last verified
- Nov 2015
- First submitted
- 22 Jan 2015
- Last updated
- 25 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fat Induced Insulin Resistance and Atherosclerosis
- ClinicalTrials.gov ID
- NCT02348190
- Acronym / sponsor ID
- 4148
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Temple UniversityUniversity, hospital or other
- Study start
- Jun 2003
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 28 Jan 2015 (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 overall objective of the current proposal is to strengthen the putative link between FFA induced insulin resistance and atherosclerotic vascular disease (ASVD). To this end, the investigators will test the following hypotheses: 1) that FFA induced activation of protein kinase C βII (PKC β II) and δ and other serine kinases such as IκB kinase (IKK) in human muscle is associated with a decrease in insulin stimulated tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and of IRS-1 associated phosphatidylinositol 3 (PI3) kinase; 2) that these changes precede the development of insulin resistance; 3) that the decrease in IκB-α results in activation of nuclear factor κB (NFκB) and the expression of adhesion molecules and cytokines; 4) that PKC and IKK are involved in producing insulin resistance and activation of the IκB/ NFκB pathway and lastly 5) that the same mechanisms operative in healthy volunteers are also operative in patients with T2DM.The investigators will test these hypotheses in normal (current) and diabetic volunteers (previously completed) . Euglycemic-hyperinsulinemic clamps will be performed with and without co-infusion of lipid plus heparin (to raise FFAs) and by obtaining serial muscle and fat biopsies and blood samples will be obtained for measurement of substrates, hormones, enzymes and metabolites.
Detailed description
All subjects will be admitted to the GCRC in the afternoon before the tests (Day 1) and will undergo a thorough physical examination. Routine admission lab tests (including a 2-h 75g OGTT) and body composition measurements will be obtained. A standardized dinner will be served at ~ 6PM. The next (Day 2) after an overnight fast, IV lines will be placed (arms will be wrapped with a heating blanket and kept at 70ºF to arterialize venous blood).
The following studies will be performed.
Thirty-two healthy volunteers will undergo euglycemic - hyperinsulinemic clamping without radioactive isotopes and with (n=16) and without (n=16) lipid/heparin co-infusion for 8 hours.
Serial (at 0, 1, 2 and 4 h) muscle and fat biopsies and serial blood samples (q' 1 h) will be obtained. The following measurements will be obtained in muscle biopsies and T-cell extracts: PKC-βI and II and PKC-δ, IKK, IκB-α, NFκB, IRS-1 tyrosine phosphorylation, IRS-1 associated PI3- kinase, ICAM, VCAM and e-selectin mRNAs.
Study design
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lipid/heparin | Active comparator | Other: Lipid/heparin16 healthy volunteers will undergo euglycemic - hyperinsulinemic clamping without radioactive isotopes and with (n=16) lipid/heparin co-infusion for 8 hours. |
| Control | Placebo comparator | Other: Lipid/heparin16 healthy volunteers will undergo euglycemic - hyperinsulinemic clamping without radioactive isotopes and without (n=16) lipid/heparin co-infusion for 8 hours. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- The investigators plan to study 32 healthy normal subjects.
- These volunteers will be male and female, between the ages of 30 and 75 years and of all races.
- None of these volunteers will have a family history of diabetes or any other endocrine disorder and none will be taking any medications.
Key exclusion criteria (2 listed)
- Patients with chronic health problems including cardiovascular, pulmonary, hematologic (*Hb< 9 g/dl), renal (serum creatinine > 1.8 mg/dl), hepatic disease, AIDS or other chronic infectious disease will be excluded.
- Pregnant women will be excluded. Non-pregnant women will be studied during the follicular phase of their menstrual cycle. If needed, a pregnancy test will be performed to exclude pregnancy.
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 |
|---|---|---|
| Lipid/heparin32 healthy volunteers will undergo euglycemic - hyperinsulinemic clamping without radioactive isotopes and with (n=16) and without (n=16) lipid/heparin co-infusion for 8 hours. Serial (at 0, 1, 2 and 4 h) muscle and fat biopsies and serial blood samples (q' 1 h) will be obtained. The following measurements will be obtained in muscle biopsies and T-cell extracts: PKC-βI and II and PKC-δ, IKK, IκB-α, NFκB, IRS-1 tyrosine phosphorylation, IRS-1 associated PI3- kinase, ICAM, VCAM and e-selectin mRNAs. | Other | Control, Lipid/heparin |
Primary outcome
protein kinase C enzyme activity in tissue samples
Time frame: baseline, 1 hour, 2 hour, 4 hours
The following measurements will be obtained in muscle biopsies: PKC-βI and II and PKC-δ, IKK, IκB-α, NFκB, IRS-1 tyrosine phosphorylation, IRS-1 associated PI3- kinase, ICAM, VCAM and e-selectin mRNAs.
3 secondary outcomes
Insulin sensitivity
Time frame: 0, 1, 2, 3, 4, 5, 6, 7, 8 hours
Free fatty acids
Time frame: 0, 1 2, 3, 4, 5, 6, 7 ,8 hours
protein kinase C enzyme activity in T cells
Time frame: 0, 1, 2, 3, 4, 5, 6, 7, 8 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 25 Nov 2015.
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.
Guenther Boden, MD principal investigator
Temple University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lipid/heparin in people with Other Fatty Acid Oxidation Disorders and Diabetes Mellitus, run by Temple University 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 3 inclusion and 2 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 25 Nov 2015. 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?
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?
protein kinase C enzyme activity in tissue samples (time frame: baseline, 1 hour, 2 hour, 4 hours). 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 25 Nov 2015.