Insulin ResistanceNCT00833846
Pilot Study of Mitochondrial Biology in Human Platelets
An observational study of Insulin Resistance and Diabetes, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Type II diabetes mellitus is rapidly becoming a global pandemic with a deleterious impact on cardiovascular morbidity and mortality. Understanding its pathophysiology is important for the development of future therapeutic interventions. Read more about this study
- Who is it for?
- Ages 21 to 60 years
- Conditions the study is for
- Insulin Resistance, Diabetes
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jan 2009to 24 Oct 2011
- 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 21 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Adults older than 21 years and less than 40 years.
- Insulin sensitivity with a fasting glucose less than 100 mg/dl and a 2-hour post oral glucose tolerance test blood glucose less than 140 mg/dl.
- Subject understands protocol and provides written, informed consent.
- Adults older than 21 years and less than 40 years.
- Insulin resistance as defined by a fasting blood sugar of greater than or equal to 100mg/dl but less than 125 mg/dl and/or a 2-hour post oral glucose tolerance test blood glucose greater than 140 mg/dl and less than 200 mg/dl.
- Subject understands protocol and provides written, informed consent.
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- Adults greater than or equal to 40 years and less than or equal to 60 years.
- Insulin sensitivity with a fasting blood glucose less than 100 mg/dl and a 2-hour post oral glucose tolerance test blood glucose less than 140 mg/dl.
- Subject understands protocol and provides written, informed consent.
- Adults greater than or equal to 40 years and less than or equal to 60 years.
- Insulin resistance as defined by a fasting blood sugar of greater than or equal to 100mg/dl but less than 125 mg/dl and/or a 2-hour post oral glucose tolerance test blood glucose greater than 140 mg/dl and less than 200 mg/dl.
- Subject understands protocol and provides written, informed consent.
- Adults greater than or equal to 40 years and less than or equal to 60 years.
- Type II diabetes as defined by a fasting blood sugar of greater than 125 mg/dl and/or a 2-hour post oral glucose tolerance test blood glucose greater than 200 mg/dl if untreated and/or if subjects are on oral hypoglycemic agent therapy where the HbA1c is greater than 6.7 percent.
- Subject understands protocol and provides written, informed consent.
Who cannot join
- Uncontrolled hypertension, heart failure, unstable coronary artery disease or symptomatic peripheral arterial disease requiring changes in medication or medical intervention in the preceding 3 months.
- Insulin-dependant diabetes mellitus or current use of thiazolidinediones.
- Women of childbearing age unless recent pregnancy test is negative and are not breast feeding.
- Serum creatinine greater than 2.5 mg/dl.
- Liver transaminase levels greater than 2.5 times upper limit of normal.
- History of cancer treated with chemotherapy or irradiation in the last 5 years.
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- Active inflammatory disease, or infection, or abnormal white blood cell differential.
- Enrollment in any drug studies within the last 30 days.
- BMI greater than 35 for the middle age groups and greater than 30 for the younger subjects.
- Age greater than 60 years.
- Another member of a potential study subject's immediate family has been recruited/participated in this study.
- The use of anticoagulation therapy, thiazide diuretics, corticosteroids, or some psychiatric drugs that cannot be stopped for medical reasons for a few days for study participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Type II diabetes mellitus is rapidly becoming a global pandemic with a deleterious impact on cardiovascular morbidity and mortality. Understanding its pathophysiology is important for the development of future therapeutic interventions. Emerging evidence suggests interplay between mitochondrial dysfunction and the development of insulin resistance. Interestingly, mitochondrial dysfunction in skeletal muscle and adipose tissue are early events in the development of type II diabetes mellitus and are proposed to play a role in exacerbating insulin resistance. Although it has been demonstrated that skeletal muscle of insulin-resistant individuals has reduced mitochondria and mitochondrial dysfunction, whether this disruption of mitochondrial function is more widespread has not been explored. We hypothesize that this disruption of mitochondrial function is more systemic and thereby may contribute to the development of peripheral insulin resistance and possibly promote the myriad of complications associated with diabetes.
To test these assumptions, we propose an initial proof of concept study to evaluate mitochondrial biology in human platelets in normal volunteers, pre-diabetic and diabetic subjects to assess whether mitochondrial disruption/dysfunction evolves with the progression to type II diabetes. In parallel, proteomic analysis will be performed to evaluate whether the development of insulin resistance and diabetes confers a specific modulation in the biological signature of human platelets with disease progression. To delineate these concepts, we will evaluate study subject's glucose tolerance and insulin sensitivity and draw blood in parallel to study their platelets. Biological readouts will include: 1) the quantification of the mitochondrial proteome and electron transfer chain content; 2) the evaluation of platelet mitochondrial respiratory function and 3) to determine the mitochondrial reactive oxygen species capacity and defenses. If this hypothesis is validated, this study will show that the mitochondrial disruption/dysfunction is a more generalized finding in type II diabetes. Additionally, it would propose the use of platelets as potential biomarkers for early detection of mitochondrial function and assessment of disease. Finally, this would establish a peripheral blood readout of the modification of mitochondrial function as a novel approach to monitor the prevention and/or reversal of insulin resistance and diabetes in response to therapeutic strategies.
Read the detailed description
Type II diabetes mellitus is rapidly becoming a global pandemic with a deleterious impact on cardiovascular morbidity and mortality. Understanding its pathophysiology is important for the development of future therapeutic interventions. Emerging evidence suggests interplay between mitochondrial dysfunction and the development of insulin resistance. Interestingly, mitochondrial dysfunction in skeletal muscle and adipose tissue are early events in the development of type II diabetes mellitus and are proposed to play a role in exacerbating insulin resistance. Although it has been demonstrated that skeletal muscle of insulin-resistant individuals has reduced mitochondria and mitochondrial dysfunction, whether this disruption of mitochondrial function is more widespread has not been explored. We hypothesize that this disruption of mitochondrial function is more systemic and thereby may contribute to the development of peripheral insulin resistance and possibly promote the myriad of complications associated with diabetes.
To test these assumptions, we propose an initial proof of concept study to evaluate mitochondrial biology in human platelets in normal volunteers, pre-diabetic and diabetic subjects to assess whether mitochondrial disruption/dysfunction evolves with the progression to type II diabetes. In parallel, proteomic analysis will be performed to evaluate whether the development of insulin resistance and diabetes confers a specific modulation in the biological signature of human platelets with disease progression. To delineate these concepts, we will evaluate study subject's glucose tolerance and insulin sensitivity and draw blood in parallel to study their platelets. Biological readouts will include: 1) the quantification of the mitochondrial proteome and electron transfer chain content; 2) the evaluation of platelet mitochondrial respiratory function and 3) to determine the mitochondrial reactive oxygen species capacity and defenses. If this hypothesis is validated, this study will show that the mitochondrial disruption/dysfunction is a more generalized finding in type II diabetes. Additionally, it would propose the use of platelets as potential biomarkers for early detection of mitochondrial function and assessment of disease. Finally, this would establish a peripheral blood readout of the modification of mitochondrial function as a novel approach to monitor the prevention and/or reversal of insulin resistance and diabetes in response to therapeutic strategies.
- Conditions
- Insulin Resistance, Diabetes
- Keywords
- Mitochondria in Platelets, Mitochondria in Diabetes, Insulin Resistance and Mitochondria, Diabetes, Insulin Resistance
- Medical subject headings
- Insulin Resistance, Diabetes Mellitus
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2009 (estimated)
- Study start27 Jan 2009
- Study completion24 Oct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Time perspective
- Prospective
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00833846
- Sponsor's protocol ID
- 090068
- Other IDs
- 09-H-0068
- Status last verified
- 24 Oct 2011
- First submitted
- 30 Jan 2009
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Barr EL, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, Cameron AJ, Dwyer T, Taylor HR, Tonkin AM, Wong TY, McNeil J, Shaw JE. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation. 2007 Jul 10;116(2):151-7. doi: 10.1161/CIRCULATIONAHA.106.685628. Epub 2007 Jun 18.
PubMed 17576864Morino K, Petersen KF, Shulman GI. Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes. 2006 Dec;55 Suppl 2(Suppl 2):S9-S15. doi: 10.2337/db06-S002.
PubMed 17130651Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science. 2005 Jan 21;307(5708):384-7. doi: 10.1126/science.1104343.
PubMed 15662004
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Mitochondrial Biology in Human Platelets
- ClinicalTrials.gov ID
- NCT00833846
- Acronym / sponsor ID
- 090068
- Conditions
- Insulin Resistance, Diabetes
- Keywords
- Mitochondria in Platelets, Mitochondria in Diabetes, Insulin Resistance and Mitochondria, Diabetes, Insulin Resistance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 27 Jan 2009
- Study completion
- 24 Oct 2011
- First posted
- 2 Feb 2009 (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.
Type II diabetes mellitus is rapidly becoming a global pandemic with a deleterious impact on cardiovascular morbidity and mortality. Understanding its pathophysiology is important for the development of future therapeutic interventions. Emerging evidence suggests interplay between mitochondrial dysfunction and the development of insulin resistance. Interestingly, mitochondrial dysfunction in skeletal muscle and adipose tissue are early events in the development of type II diabetes mellitus and are proposed to play a role in exacerbating insulin resistance. Although it has been demonstrated that skeletal muscle of insulin-resistant individuals has reduced mitochondria and mitochondrial dysfunction, whether this disruption of mitochondrial function is more widespread has not been explored. We hypothesize that this disruption of mitochondrial function is more systemic and thereby may contribute to the development of peripheral insulin resistance and possibly promote the myriad of complications associated with diabetes.
To test these assumptions, we propose an initial proof of concept study to evaluate mitochondrial biology in human platelets in normal volunteers, pre-diabetic and diabetic subjects to assess whether mitochondrial disruption/dysfunction evolves with the progression to type II diabetes. In parallel, proteomic analysis will be performed to evaluate whether the development of insulin resistance and diabetes confers a specific modulation in the biological signature of human platelets with disease progression. To delineate these concepts, we will evaluate study subject's glucose tolerance and insulin sensitivity and draw blood in parallel to study their platelets. Biological readouts will include: 1) the quantification of the mitochondrial proteome and electron transfer chain content; 2) the evaluation of platelet mitochondrial respiratory function and 3) to determine the mitochondrial reactive oxygen species capacity and defenses. If this hypothesis is validated, this study will show that the mitochondrial disruption/dysfunction is a more generalized finding in type II diabetes. Additionally, it would propose the use of platelets as potential biomarkers for early detection of mitochondrial function and assessment of disease. Finally, this would establish a peripheral blood readout of the modification of mitochondrial function as a novel approach to monitor the prevention and/or reversal of insulin resistance and diabetes in response to therapeutic strategies.
Detailed description
Type II diabetes mellitus is rapidly becoming a global pandemic with a deleterious impact on cardiovascular morbidity and mortality. Understanding its pathophysiology is important for the development of future therapeutic interventions. Emerging evidence suggests interplay between mitochondrial dysfunction and the development of insulin resistance. Interestingly, mitochondrial dysfunction in skeletal muscle and adipose tissue are early events in the development of type II diabetes mellitus and are proposed to play a role in exacerbating insulin resistance. Although it has been demonstrated that skeletal muscle of insulin-resistant individuals has reduced mitochondria and mitochondrial dysfunction, whether this disruption of mitochondrial function is more widespread has not been explored. We hypothesize that this disruption of mitochondrial function is more systemic and thereby may contribute to the development of peripheral insulin resistance and possibly promote the myriad of complications associated with diabetes.
To test these assumptions, we propose an initial proof of concept study to evaluate mitochondrial biology in human platelets in normal volunteers, pre-diabetic and diabetic subjects to assess whether mitochondrial disruption/dysfunction evolves with the progression to type II diabetes. In parallel, proteomic analysis will be performed to evaluate whether the development of insulin resistance and diabetes confers a specific modulation in the biological signature of human platelets with disease progression. To delineate these concepts, we will evaluate study subject's glucose tolerance and insulin sensitivity and draw blood in parallel to study their platelets. Biological readouts will include: 1) the quantification of the mitochondrial proteome and electron transfer chain content; 2) the evaluation of platelet mitochondrial respiratory function and 3) to determine the mitochondrial reactive oxygen species capacity and defenses. If this hypothesis is validated, this study will show that the mitochondrial disruption/dysfunction is a more generalized finding in type II diabetes. Additionally, it would propose the use of platelets as potential biomarkers for early detection of mitochondrial function and assessment of disease. Finally, this would establish a peripheral blood readout of the modification of mitochondrial function as a novel approach to monitor the prevention and/or reversal of insulin resistance and diabetes in response to therapeutic strategies.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Adults older than 21 years and less than 40 years.
- Insulin sensitivity with a fasting glucose less than 100 mg/dl and a 2-hour post oral glucose tolerance test blood glucose less than 140 mg/dl.
- Subject understands protocol and provides written, informed consent.
- Adults older than 21 years and less than 40 years.
- Insulin resistance as defined by a fasting blood sugar of greater than or equal to 100mg/dl but less than 125 mg/dl and/or a 2-hour post oral glucose tolerance test blood glucose greater than 140 mg/dl and less than 200 mg/dl.
Key exclusion criteria (12 listed)
- Uncontrolled hypertension, heart failure, unstable coronary artery disease or symptomatic peripheral arterial disease requiring changes in medication or medical intervention in the preceding 3 months.
- Insulin-dependant diabetes mellitus or current use of thiazolidinediones.
- Women of childbearing age unless recent pregnancy test is negative and are not breast feeding.
- Serum creatinine greater than 2.5 mg/dl.
- Liver transaminase levels greater than 2.5 times upper limit of normal.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 17576864Barr EL, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, Cameron AJ, Dwyer T, Taylor HR, Tonkin AM, Wong TY, McNeil J, Shaw JE. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation. 2007 Jul 10;116(2):151-7. doi: 10.1161/CIRCULATIONAHA.106.685628. Epub 2007 Jun 18.
- Background: PubMed 17130651Morino K, Petersen KF, Shulman GI. Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes. 2006 Dec;55 Suppl 2(Suppl 2):S9-S15. doi: 10.2337/db06-S002.
- Background: PubMed 15662004Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science. 2005 Jan 21;307(5708):384-7. doi: 10.1126/science.1104343.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site 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 and Diabetes, run by National Heart, Lung, and Blood Institute (NHLBI) 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 15 inclusion and 12 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 2 Jul 2017. 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. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00833846, which also lists 3 linked publications.
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 2 Jul 2017.