Insulin ResistanceNCT03731598
Ceramides in Muscle During Insulin Resistance
An observational study of Insulin Resistance, run by University of Utah at 2 sites in United States.
Trial summary
Overnutrition and physical inactivity promote the accumulation of sphingolipids such as ceramides which block insulin signaling and anabolic metabolism. Implementation of pharmacological or genetic interventions to reduce sphingolipid levels in rodents prevents or reverses an impressive array of metabolic pathologies… Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance
- What is being tested?
- bed rest
- Type of treatment
- Surgery or procedure
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 May 2018to Jan 2022
- Phase
- Observational
- 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 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy older community dwelling participants in salt lake city and surrounding cities
Who may be able to join
- Age between 60 yrs and older
- Ability to sign informed consent
- Free-living, prior to admission
Who cannot join
- Cardiac abnormalities considered exclusionary by the study physician
- Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes)
- Globular filtration rate <65 mL/min/1.73m2 or evidence of kidney disease or failure
- Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes, hypercholesterolemia > 250 mg/dl, claudication or evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal and pedal arteries)
- Risk of deep vein thrombosis including family history of thrombophilia, deep vein thrombosis, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb>18 g/dL) or thrombocytosis (platelets>400x103/mL), and connective tissue diseases (positive lupus anticoagulant), hyperhomocysteinemia, deficiencies of factor V Leiden, proteins S and C, and antithrombin III
- Use of anticoagulant therapy (e.g., Coumadin, heparin)
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- Elevated systolic pressure >150 or a diastolic blood pressure > 100
- Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
- Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
- Inability to abstain from smoking for duration of study
- A history of > 20 pack per year smoking
- HIV or hepatitis B or C
- Recent anabolic or corticosteroids use (within 3 months)
- Subjects with hemoglobin or hematocrit lower than accepted lab values
- Agitation/aggression disorder (by psychiatric history and exam)
- History of stroke with motor disability
- A recent history (<12 months) of gastrointestinal bleed
- Liver disease
- Respiratory disease (acute upper respiratory infection, history of chronic lung disease with resting oxygen saturation <97% on room air)
- Any other condition or event considered exclusionary by the PI and faculty physician
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Utah
Salt Lake City, Utah, 84108
The University of Utah
Salt Lake City, Utah, 84112
About this study
Official title: The Role of Ceramides in Skeletal Muscle
Overnutrition and physical inactivity promote the accumulation of sphingolipids such as ceramides which block insulin signaling and anabolic metabolism. Implementation of pharmacological or genetic interventions to reduce sphingolipid levels in rodents prevents or reverses an impressive array of metabolic pathologies (e.g. insulin resistance, diabetes, steatohepatitis, hypertension, cardiomyopathy, and atherosclerosis). To elucidate the tissue-specific mechanisms through which ceramides contribute to these diseases, mice have been produced to allow for the conditional, cell-type restricted ablation of enzymes required for ceramide biosynthesis or degradation (i.e. serine palmitoyltransferase and dihydroceramide desaturases-1) or degradation (i.e. acid ceramidase). Aims of the project include the following: To use these novel mouse models to evaluate the effect of muscle-specific ceramide depletion or induction on insulin sensitivity, muscle growth, and genomic/proteomic signatures under conditions of overnutrition and inactivity. To apply a ceramide flux assay in isolated human myotubes to identify the regulatory mechanisms that influence rates of ceramide biosynthesis; and, To determine the efficacy of a new class of inhibitors of dihydroceramide desaturases-1, our preferred target in the ceramide synthesis pathway, as therapeutics that improve muscle insulin sensitivity and prevent muscle loss in rodents. Findings obtained from these studies could uncover new nutrient-sensing machinery that modulates insulin sensitivity and muscle growth. Moreover, the translational component could lead to new pharmacological approaches for improving muscle health.
Read the detailed description
Healthy, insulin sensitive, physically active male and female adults will be studied (N=15; 65-80 years as determined by sample size calculation below) recruited from the Salt Lake City area. Inclusion and exclusion criteria can be found in Protection of Human Subjects. Outpatient blood screening, including an oral glucose tolerance (OGTT) test, and bed rest experiments will take place in the University Center for Clinical and Translational Sciences (CCTS), a clinical service supported by an NIH Clinical and Translational Science Award. The CCTS medical supervising physician oversees procedures. Participants will arrive at the CCTS fasted on Day 1 and a euglycemic-hyperinsulinemic clamp study will be performed as done previously with this unit. Vastus lateralis muscle biopsies will be obtained before and three hours after the clamp. Periodic blood samples will be obtained as part of the clamp procedure for measurement of insulin and glucose. Muscle samples will be either cultured or flash-frozen in liquid nitrogen and stored for later analysis. After completion of the first insulin clamp experiment (Day 1), subjects will adhere to 5-days of strict bed rest as this is a clinically-relevant time frame for older adults hospitalized for acute medical illness, as well as being sufficient to induced insulin resistance. Established safety and comfort guidelines will be followed as done previously. On Day 5, after an overnight fast, a second insulin clamp study will be conducted and muscle biopsies will be again obtained.
- Conditions
- Insulin Resistance
- Being tested
- bed rest
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bed restProcedure or surgery
Volunteers will be physically inactive on bed rest at the clinical research center
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin resistance
Steady state glucose infusion rate in response to constant insulin will be determined by a 3-hour hyperinsulinemic-euglycemic clamp procedure.
Measured: Change in glucose infusion rate at Day 5 of bed rest (from Pre bed rest)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2018
- Study start1 May 2018
- Primary completionJan 2022 (estimated)
- Study completionJan 2022 (estimated)
Why it stopped: Difficulty recruiting. Objectives from this protocol added to another protocol collecting the same information.
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 University of UtahThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Micah Drummond, University of Utah
- Investigators
- Scott Summers, PhD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03731598
- Sponsor's protocol ID
- DK115824
- Status last verified
- Jun 2022
- First submitted
- 2 Nov 2018
- Last updated
- 22 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We will provide access to all data collected as a part of this research. Investigators may request access to the shared data generated by this study. All external investigators must submit a written request identifying the research question they are examining and specifying the data they are interested in receiving. The request must include a data security plan and explanation of how the data will be stored and who will have access to the data. All requests will be reviewed by Drs. Summers and Drummond to be sure appropriate NIH requirements are followed.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Ceramides in Skeletal Muscle
- ClinicalTrials.gov ID
- NCT03731598
- Acronym / sponsor ID
- DK115824
- Conditions
- Insulin Resistance
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Difficulty recruiting. Objectives from this protocol added to another protocol collecting the same information.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- 1 May 2018 (actual)
- Primary completion
- Jan 2022 (estimated)
- Study completion
- Jan 2022 (estimated)
- First posted
- 6 Nov 2018 (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.
Overnutrition and physical inactivity promote the accumulation of sphingolipids such as ceramides which block insulin signaling and anabolic metabolism. Implementation of pharmacological or genetic interventions to reduce sphingolipid levels in rodents prevents or reverses an impressive array of metabolic pathologies (e.g. insulin resistance, diabetes, steatohepatitis, hypertension, cardiomyopathy, and atherosclerosis). To elucidate the tissue-specific mechanisms through which ceramides contribute to these diseases, mice have been produced to allow for the conditional, cell-type restricted ablation of enzymes required for ceramide biosynthesis or degradation (i.e. serine palmitoyltransferase and dihydroceramide desaturases-1) or degradation (i.e. acid ceramidase). Aims of the project include the following: To use these novel mouse models to evaluate the effect of muscle-specific ceramide depletion or induction on insulin sensitivity, muscle growth, and genomic/proteomic signatures under conditions of overnutrition and inactivity. To apply a ceramide flux assay in isolated human myotubes to identify the regulatory mechanisms that influence rates of ceramide biosynthesis; and, To determine the efficacy of a new class of inhibitors of dihydroceramide desaturases-1, our preferred target in the ceramide synthesis pathway, as therapeutics that improve muscle insulin sensitivity and prevent muscle loss in rodents. Findings obtained from these studies could uncover new nutrient-sensing machinery that modulates insulin sensitivity and muscle growth. Moreover, the translational component could lead to new pharmacological approaches for improving muscle health.
Detailed description
Healthy, insulin sensitive, physically active male and female adults will be studied (N=15; 65-80 years as determined by sample size calculation below) recruited from the Salt Lake City area. Inclusion and exclusion criteria can be found in Protection of Human Subjects. Outpatient blood screening, including an oral glucose tolerance (OGTT) test, and bed rest experiments will take place in the University Center for Clinical and Translational Sciences (CCTS), a clinical service supported by an NIH Clinical and Translational Science Award. The CCTS medical supervising physician oversees procedures. Participants will arrive at the CCTS fasted on Day 1 and a euglycemic-hyperinsulinemic clamp study will be performed as done previously with this unit. Vastus lateralis muscle biopsies will be obtained before and three hours after the clamp. Periodic blood samples will be obtained as part of the clamp procedure for measurement of insulin and glucose. Muscle samples will be either cultured or flash-frozen in liquid nitrogen and stored for later analysis. After completion of the first insulin clamp experiment (Day 1), subjects will adhere to 5-days of strict bed rest as this is a clinically-relevant time frame for older adults hospitalized for acute medical illness, as well as being sufficient to induced insulin resistance. Established safety and comfort guidelines will be followed as done previously. On Day 5, after an overnight fast, a second insulin clamp study will be conducted and muscle biopsies will be again obtained.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy older community dwelling participants in salt lake city and surrounding cities
Key inclusion criteria (3 listed)
- Age between 60 yrs and older
- Ability to sign informed consent
- Free-living, prior to admission
Key exclusion criteria (20 listed)
- Cardiac abnormalities considered exclusionary by the study physician
- Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes)
- Globular filtration rate <65 mL/min/1.73m2 or evidence of kidney disease or failure
- Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes, hypercholesterolemia > 250 mg/dl, claudication or evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal and pedal arteries)
- Risk of deep vein thrombosis including family history of thrombophilia, deep vein thrombosis, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb>18 g/dL) or thrombocytosis (platelets>400x103/mL), and connective tissue diseases (positive lupus anticoagulant), hyperhomocysteinemia, deficiencies of factor V Leiden, proteins S and C, and antithrombin III
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 |
|---|---|---|
| bed restVolunteers will be physically inactive on bed rest at the clinical research center | Procedure or surgery | – |
Primary outcome
Insulin resistance
Time frame: Change in glucose infusion rate at Day 5 of bed rest (from Pre bed rest)
Steady state glucose infusion rate in response to constant insulin will be determined by a 3-hour hyperinsulinemic-euglycemic clamp procedure.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2022.
- Individual participant dataSharing planned: No. We will provide access to all data collected as a part of this research. Investigators may request access to the shared data generated by this study. All external investigators must submit a written request identifying the research question they are examining and specifying the data they are interested in receiving. The request must include a data security plan and explanation of how the data will be stored and who will have access to the data. All requests will be reviewed by Drs. Summers and Drummond to be sure appropriate NIH requirements are followed.
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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.
Scott Summers, PhD principal investigator
University of Utah
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Insulin Resistance, run by University of Utah 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 3 inclusion and 20 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: withdrawn, as of the sponsor's last update on 22 Jun 2022. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Insulin resistance (time frame: Change in glucose infusion rate at Day 5 of bed rest (from Pre bed rest)). 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 2022.