Insulin ResistanceEarly Phase 1DYNAMMO-T2DNCT02697201
Dynamics of Muscle Mitochondria in Type 2 Diabetes (DYNAMMO T2D)
A Early Phase 1 study testing Intralipid and Saline in people with Insulin Resistance, run by Pennington Biomedical Research Center at 1 site in United States.
Trial summary
Insulin promotes the clearance of sugars from the blood into skeletal muscle and fat cells for use as energy; it also promotes storage of excess nutrients as fat. Type 2 diabetes occurs when the cells of the body become resistant to the effects of insulin, and this causes high blood sugar and contributes to a build-up… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance
- What is being tested?
- Intralipid and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2016to May 2021
- Phase
- Early Phase 1
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy
- Sedentary
- Normal glucose tolerance
- BMI <25 kg/m2
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Pennington Biomedical Research Center
Baton Rouge, Louisiana, 70808
About this study
Official title: Dynamics of Muscle Mitochondria in Type 2 Diabetes (DYNAMMO-T2D)
Insulin promotes the clearance of sugars from the blood into skeletal muscle and fat cells for use as energy; it also promotes storage of excess nutrients as fat. Type 2 diabetes occurs when the cells of the body become resistant to the effects of insulin, and this causes high blood sugar and contributes to a build-up of fat in muscle, pancreas, liver, and the heart. Understanding how insulin resistance occurs will pave the way for new therapies aimed at preventing and treating type 2 diabetes.
Mitochondria are cellular structures that are responsible for turning nutrients from food, into the energy that our cells run on. As a result, mitochondria are known as "the powerhouse of the cell." Mitochondria are dynamic organelles that can move within a cell to the areas where they are needed, and can fuse together to form large, string-like, tubular networks or divide into small spherical structures. The name of this process is "mitochondrial dynamics" and the process keeps the cells healthy. However, when more food is consumed compared to the amount of energy burned, mitochondria may become overloaded and dysfunctional resulting in a leak of partially metabolized nutrients that can interfere with the ability of insulin to communicate within the cell. This may be a way for the cells to prevent further uptake of nutrients until the current supply has been exhausted. However, long term overload of the mitochondria may cause blood sugar levels to rise and lead to the development of type 2 diabetes.
This study will provide information about the relationship between mitochondrial dynamics, insulin resistance and type 2 diabetes.
Read the detailed description
The traditional view of mitochondria as isolated, spherical, energy producing organelles is undergoing a revolutionary transformation. Emerging data show that mitochondria form a dynamic networked reticulum that is regulated by cycles of fission and fusion. The discovery of a number of proteins that regulate these activities has led to important advances in understanding human disease. Data show that activation of dynamin related protein 1 (Drp1), a protein that controls mitochondrial fission, is reduced following exercise in prediabetes, and the decrease is linked to increased insulin sensitivity and fat oxidation. The proposed research will test the hypothesis that mitochondrial dynamics is a key mechanism of insulin resistance in type 2 diabetes. Translational first-in-man studies will use an acute lipid challenge to investigate the physiological significance of altered skeletal muscle mitochondrial dynamics on insulin sensitivity in humans. The experimental approach harnesses innovative molecular and cellular tools, interfaced with physiologically significant human studies to obtain meaningful data on insulin resistance, and has the potential to generate insights that will lead to new diabetes therapies for future generations.
- Conditions
- Insulin Resistance
- Being tested
- Intralipid, Saline
- Keywords
- Mitochondrial Dynamics, Insulin Resistance
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IntralipidDrug
Also called Liposyn
0.55 ml/kg/h
SalineDrug
0.55 ml/kg/h for
| Study group | Role | What they receive |
|---|---|---|
| Intralipid Infusion, then Saline | Experimental | Participants in this arm will first receive a lipid infusion. Then 4 weeks later the saline infusion. Receives: Drug: Intralipid; Drug: Saline |
| Saline Infusion, then Intralipid | Sham comparator | Participants in this arm will first receive a saline infusion. Then 4 weeks later the lipid infusion. Receives: Drug: Intralipid; Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of lipid infusion on mitochondrial fission
Fission will be assessed from quantitative measures of dynamin-related protein-1. The unit of assessment is arbitrary units of blot intensity and is expressed as AU.
Measured: 5 years
Secondary outcomes (2)
Effects of lipid infusion on mitochondrial function
Function will be assessed from oxygen consumption. Unit of assessment is pmol/s/mg of muscle.
Measured: 5 years
Insulin sensitivity
Insulin sensitivity will be assessed by euglycemic hyperinsulinemic clamp. Units of assessment are mg/kg/min.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2016 (estimated)
- Study startJul 2016
- Primary completionMay 2021
- Study completionMay 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Insulin ResistanceStudies 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pennington Biomedical Research Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Kirwan, Pennington Biomedical Research Center
- Investigators
- John P Kirwan, Ph.D., Principal investigator, Pennington Biomedical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02697201
- Sponsor's protocol ID
- 15-1311
- Acronym
- DYNAMMO-T2D
- Status last verified
- Jul 2021
- First submitted
- 18 Feb 2016
- Last updated
- 27 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Axelrod CL, Fealy CE, Erickson ML, Davuluri G, Fujioka H, Dantas WS, Huang E, Pergola K, Mey JT, King WT, Mulya A, Hsia D, Burguera B, Tandler B, Hoppel CL, Kirwan JP. Lipids activate skeletal muscle mitochondrial fission and quality control networks to induce insulin resistance in humans. Metabolism. 2021 Aug;121:154803. doi: 10.1016/j.metabol.2021.154803. Epub 2021 Jun 4.
PubMed 34090870
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamics of Muscle Mitochondria in Type 2 Diabetes (DYNAMMO-T2D)
- ClinicalTrials.gov ID
- NCT02697201
- Acronym / sponsor ID
- DYNAMMO-T2D / 15-1311
- Conditions
- Insulin Resistance
- Keywords
- Mitochondrial Dynamics, Insulin Resistance
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Pennington Biomedical Research CenterUniversity, hospital or other
- Study start
- Jul 2016
- Primary completion
- May 2021 (actual)
- Study completion
- May 2021 (actual)
- First posted
- 3 Mar 2016 (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.
Insulin promotes the clearance of sugars from the blood into skeletal muscle and fat cells for use as energy; it also promotes storage of excess nutrients as fat. Type 2 diabetes occurs when the cells of the body become resistant to the effects of insulin, and this causes high blood sugar and contributes to a build-up of fat in muscle, pancreas, liver, and the heart. Understanding how insulin resistance occurs will pave the way for new therapies aimed at preventing and treating type 2 diabetes.
Mitochondria are cellular structures that are responsible for turning nutrients from food, into the energy that our cells run on. As a result, mitochondria are known as "the powerhouse of the cell." Mitochondria are dynamic organelles that can move within a cell to the areas where they are needed, and can fuse together to form large, string-like, tubular networks or divide into small spherical structures. The name of this process is "mitochondrial dynamics" and the process keeps the cells healthy. However, when more food is consumed compared to the amount of energy burned, mitochondria may become overloaded and dysfunctional resulting in a leak of partially metabolized nutrients that can interfere with the ability of insulin to communicate within the cell. This may be a way for the cells to prevent further uptake of nutrients until the current supply has been exhausted. However, long term overload of the mitochondria may cause blood sugar levels to rise and lead to the development of type 2 diabetes.
This study will provide information about the relationship between mitochondrial dynamics, insulin resistance and type 2 diabetes.
Detailed description
The traditional view of mitochondria as isolated, spherical, energy producing organelles is undergoing a revolutionary transformation. Emerging data show that mitochondria form a dynamic networked reticulum that is regulated by cycles of fission and fusion. The discovery of a number of proteins that regulate these activities has led to important advances in understanding human disease. Data show that activation of dynamin related protein 1 (Drp1), a protein that controls mitochondrial fission, is reduced following exercise in prediabetes, and the decrease is linked to increased insulin sensitivity and fat oxidation. The proposed research will test the hypothesis that mitochondrial dynamics is a key mechanism of insulin resistance in type 2 diabetes. Translational first-in-man studies will use an acute lipid challenge to investigate the physiological significance of altered skeletal muscle mitochondrial dynamics on insulin sensitivity in humans. The experimental approach harnesses innovative molecular and cellular tools, interfaced with physiologically significant human studies to obtain meaningful data on insulin resistance, and has the potential to generate insights that will lead to new diabetes therapies for future generations.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intralipid Infusion, then Saline | Experimental | Drug: Intralipid, Drug: SalineParticipants in this arm will first receive a lipid infusion. Then 4 weeks later the saline infusion. |
| Saline Infusion, then Intralipid | Sham comparator | Drug: Intralipid, Drug: SalineParticipants in this arm will first receive a saline infusion. Then 4 weeks later the lipid infusion. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy
- Sedentary
- Normal glucose tolerance
- BMI <25 kg/m2
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| IntralipidAlso: Liposyn0.55 ml/kg/h | Drug | Intralipid Infusion, then Saline, Saline Infusion, then Intralipid |
| Saline0.55 ml/kg/h for | Drug | Intralipid Infusion, then Saline, Saline Infusion, then Intralipid |
Primary outcome
Effects of lipid infusion on mitochondrial fission
Time frame: 5 years
Fission will be assessed from quantitative measures of dynamin-related protein-1. The unit of assessment is arbitrary units of blot intensity and is expressed as AU.
2 secondary outcomes
Effects of lipid infusion on mitochondrial function
Time frame: 5 years
Insulin sensitivity
Time frame: 5 years
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 27 Jul 2021.
- Derived from this study: PubMed 34090870Axelrod CL, Fealy CE, Erickson ML, Davuluri G, Fujioka H, Dantas WS, Huang E, Pergola K, Mey JT, King WT, Mulya A, Hsia D, Burguera B, Tandler B, Hoppel CL, Kirwan JP. Lipids activate skeletal muscle mitochondrial fission and quality control networks to induce insulin resistance in humans. Metabolism. 2021 Aug;121:154803. doi: 10.1016/j.metabol.2021.154803. Epub 2021 Jun 4.
- 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.
John P Kirwan, Ph.D. principal investigator
Pennington Biomedical Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Intralipid and Saline in people with Insulin Resistance, run by Pennington Biomedical Research 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 4 inclusion and 0 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 27 Jul 2021. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Effects of lipid infusion on mitochondrial fission (time frame: 5 years). 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 NCT02697201, 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 27 Jul 2021.