HealthyMetPheNCT01298375
Metabolic Phenotyping in Humans
An observational study of Healthy and Obesity, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Type 2 diabetes (T2D) is a global burden disease affecting almost 200 million people and is expected to nearly double by 2030 (1). It is imperative that this disease is kept under control, and that we begin to reverse the direction of its incidence. Read more about this study
- Who is it for?
- Ages 18 to 70 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy, Obesity, Type 2 Diabetes Mellitus
- How many people
- 132 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2011to Mar 2024
- 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 18 to 70 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Human volunteers from the surrounding area
General Inclusion criteria:
- Male sex
- Generally healthy with specifically no known cardiovascular disease or gastric ulcers, which can affect the study parameters
- Stable dietary habits (no weight loss/gain > 3 kg in the last 6 months)
Group 1, type 2 diabetes participants:
- Ages 40-70 years
- BMI > 30 kg/m2
- Non-insulin dependent type 2 diabetes
- Must be on sulphonylurea (SU)-derivate or metformin therapy for at least six months with a constant dose for at least two months, or on dietary treatment for at least six months
- Well-controlled diabetes: HbA1c < 8%
- No diabetes related co-morbidities like cardiovascular diseases, diabetic foot, polyneuropathy, retinopathy
Group 2, obese healthy control participants:
- Ages 40-70 years
- BMI > 30 kg/m2
- A plasma glucose level lower than 6.1 mmol/L
- No family history of diabetes
- No medication use
- Sedentary lifestyle; No participation in any physical activity for at least 2 years
Group 3, endurance trained athletes:
- Ages 18-35 years
- BMI < 25 kg/m2
- No family history of diabetes
- No medication use
- VO2max > 55ml/kg/min
- Active in competitive endurance-exercise activities, 3 times a week for at least 2 years
- Stable level of training for at least 6 months
Group 4, lean healthy sedentary control participants:
- Ages 18-35 years
- BMI < 25 kg/m2
- No family history of diabetes
- No medication use
- VO2max < 55ml/kg/min
- Plasma glucose < 6.1 mmol/L
- Sedentary lifestyle; No participation in physical activity for more than 1 hour per week for at least 2 years
General Exclusion criteria:
- Regular smokers
- Participation in other studies
- Female sex
- Insulin dependent diabetic individuals
- Participants with diabetes related diseases (diabetic foot, diabetic polyneuropathy, diabetic retinopathy etc.)
- Use of Thiazolidines (glitazone/rosiglitazone/pioglitazone/troglitazone)
- Use of anti-coagulants (not thrombocyte-aggregation inhibitors)
- Aberrant ECG (with signs of ischemia or cardiac failure or arrythmias)
- Weight gain/loss > 3 kg in the last 6 months
- HbA1c < 7.8 in type 2 diabetic individuals
- Contraindications for MRS scans:
- Electronic implants such as pacemakers or neurostimulator
- Iron-containing foreign bodies in eyes or brain
- Some hearing aids and artificial (heart) valves which are contraindicated for MRS
- Claustrophobia
- Participants, who do not want to be informed about unexpected medical findings, or do not wish that their physician be informed, cannot participate in the study.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Maastricht University
Maastricht, Limburg, 6200MD
Madeleen Bosma, M.S., 31433884254, m.bosma@maastrichtuniversity.nl
Lauren M Sparks, PhD
About this study
Official title: Metabolic Characterization of Type 2 Diabetic, Obese, Lean Sedentary and Endurance Trained Individuals in Vivo, ex Vivo and in Vitro
Type 2 diabetes (T2D) is a global burden disease affecting almost 200 million people and is expected to nearly double by 2030 (1). It is imperative that this disease is kept under control, and that we begin to reverse the direction of its incidence. We propose to start by identifying the physiological and molecular aspects of the problem in all spectrums of the disease (ie from insulin sensitive athletes to sedentary lean and obese individuals and further to overt type 2 diabetics), and focus our efforts on examining the differences and identifying the stages of progression for possible targets of future intervention. The proposed study "Metabolic Phenotyping" is novel in its target populations and innovative in its use of state-of-the-art techniques. We hypothesize that the in vivo differences in metabolic flexibility and mitochondrial function between endurance athletes and type 2 diabetics and their lean and obese controls are retained in vitro and will offer a new model in which to study the underlying mechanisms of the progression of T2D.
Read the detailed description
The aim of the present research proposal is to metabolically phenotype endurance trained athletes, lean and obese sedentary and type 2 diabetic individuals with the following objectives:
- assess metabolic flexibility as measured by a euglycemic-hyperinsulinemic clamp
- measure in vivo mitochondrial function by MRS of phosphocreatine (PCr) recovery
- establish primary myoblast cell lines to correlate with the above in vivo measurements, as well as further explore dietary, pharmacological and genetic manipulations in vitro
- quantify intramyocellular lipid (IMCL) and acetylcarnitine in vivo by MRS
Study population:
A total of 132 male participants (18-70 years) will participate in this study. The first group of 33 participants will be lean endurance-trained athletes, the second group will be lean sedentary control participants, the third group will be sedentary type 2 diabetic participants, and the last group of 33 participants will be obese, non-diabetic sedentary control participants. It is preferred to use male participants in order to minimize variation in the measurements by avoiding confounding factors such as hormones.
Main study parameters/endpoints: The main study parameters are differences in metabolic flexibility as measured by euglycemic-hyperinsulinemic clamp, PCr recovery, IMCL and acetylcarnitines as measured by MRS and establishment of primary myoblast cell lines for future use.
- Conditions
- Healthy, Obesity, Type 2 Diabetes Mellitus
- Keywords
- Metabolic flexibility, Mitochondrial function, Human primary myoblasts, Lipid metabolism
- Medical subject headings
- Obesity, Diabetes Mellitus, Type 2
What is being measured
The primary outcome is the main question the study is designed to answer.
Euglycemic-hyperinsulinemic clamp for measurement of insulin sensitivity and metabolic flexibility
After taking fasting blood samples, a primed constant infusion of glucose is initiated. Plasma glucose levels are clamped at ~5 mmol/L by variable co-infusion of 20% glucose. Every 5 minutes, blood is sampled for immediate determination of plasma glucose concentration. Glucose infusion rate is adjusted to obtain plasma glucose levels of ~5 mmol/L (euglycemia). A bolus of insulin is then infused. Before and during steady state, substrate oxidation is measured using an indirect calorimeter, which determines metabolic flexibility.
Measured: 10 hours
Secondary outcomes (1)
Evaluating mitochondrial function through measurement of phosphocreatine (PCr) recovery by phosphorus magnetic resonance spectroscopy (31P-MRS) within the skeletal muscle
The quantification of energy metabolites (Pi, PCr and ATP) in skeletal muscle will be performed in the v. lateralis at rest, during submaximal knee-extension exercise and during recovery. The rate at which PCr concentration is restored after exercise is an excellent in vivo measure of skeletal muscle mitochondrial oxidative capacity.
Measured: 1.5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2011 (estimated)
- Study startMar 2011
- Primary completionMar 2024 (estimated)
- Study completionMar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 132 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Patrick Schrauwen, PhD, Study director, Maastricht UniversityLauren M Sparks, PhD, Principal investigator, Maastricht UniversityMadeleen Bosma, M.S., Principal investigator, Maastricht University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01298375
- Sponsor's protocol ID
- NL35178.068.11
- Acronym
- MetPhe
- Status last verified
- Sep 2022
- First submitted
- 16 Feb 2011
- Last updated
- 19 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mancilla RF, Lindeboom L, Grevendonk L, Hoeks J, Koves TR, Muoio DM, Schrauwen P, Schrauwen-Hinderling V, Hesselink MK. Skeletal muscle mitochondrial inertia is associated with carnitine acetyltransferase activity and physical function in humans. JCI Insight. 2023 Jan 10;8(1):e163855. doi: 10.1172/jci.insight.163855.
PubMed 36413408Houzelle A, Jorgensen JA, Schaart G, Daemen S, van Polanen N, Fealy CE, Hesselink MKC, Schrauwen P, Hoeks J. Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity. Diabetologia. 2021 Feb;64(2):424-436. doi: 10.1007/s00125-020-05335-w. Epub 2020 Nov 30.
PubMed 33258025
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Characterization of Type 2 Diabetic, Obese, Lean Sedentary and Endurance Trained Individuals in Vivo, ex Vivo and in Vitro
- ClinicalTrials.gov ID
- NCT01298375
- Acronym / sponsor ID
- MetPhe / NL35178.068.11
- Conditions
- Healthy, Obesity, Type 2 Diabetes Mellitus
- Keywords
- Metabolic flexibility, Mitochondrial function, Human primary myoblasts, Lipid metabolism
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 132 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- Mar 2024 (estimated)
- Study completion
- Mar 2024 (estimated)
- First posted
- 17 Feb 2011 (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 2 diabetes (T2D) is a global burden disease affecting almost 200 million people and is expected to nearly double by 2030 (1). It is imperative that this disease is kept under control, and that we begin to reverse the direction of its incidence. We propose to start by identifying the physiological and molecular aspects of the problem in all spectrums of the disease (ie from insulin sensitive athletes to sedentary lean and obese individuals and further to overt type 2 diabetics), and focus our efforts on examining the differences and identifying the stages of progression for possible targets of future intervention. The proposed study "Metabolic Phenotyping" is novel in its target populations and innovative in its use of state-of-the-art techniques. We hypothesize that the in vivo differences in metabolic flexibility and mitochondrial function between endurance athletes and type 2 diabetics and their lean and obese controls are retained in vitro and will offer a new model in which to study the underlying mechanisms of the progression of T2D.
Detailed description
The aim of the present research proposal is to metabolically phenotype endurance trained athletes, lean and obese sedentary and type 2 diabetic individuals with the following objectives:
- assess metabolic flexibility as measured by a euglycemic-hyperinsulinemic clamp
- measure in vivo mitochondrial function by MRS of phosphocreatine (PCr) recovery
- establish primary myoblast cell lines to correlate with the above in vivo measurements, as well as further explore dietary, pharmacological and genetic manipulations in vitro
- quantify intramyocellular lipid (IMCL) and acetylcarnitine in vivo by MRS
Study population:
A total of 132 male participants (18-70 years) will participate in this study. The first group of 33 participants will be lean endurance-trained athletes, the second group will be lean sedentary control participants, the third group will be sedentary type 2 diabetic participants, and the last group of 33 participants will be obese, non-diabetic sedentary control participants. It is preferred to use male participants in order to minimize variation in the measurements by avoiding confounding factors such as hormones.
Main study parameters/endpoints: The main study parameters are differences in metabolic flexibility as measured by euglycemic-hyperinsulinemic clamp, PCr recovery, IMCL and acetylcarnitines as measured by MRS and establishment of primary myoblast cell lines for future use.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Human volunteers from the surrounding area
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
Euglycemic-hyperinsulinemic clamp for measurement of insulin sensitivity and metabolic flexibility
Time frame: 10 hours
After taking fasting blood samples, a primed constant infusion of glucose is initiated. Plasma glucose levels are clamped at ~5 mmol/L by variable co-infusion of 20% glucose. Every 5 minutes, blood is sampled for immediate determination of plasma glucose concentration. Glucose infusion rate is adjusted to obtain plasma glucose levels of ~5 mmol/L (euglycemia). A bolus of insulin is then infused. Before and during steady state, substrate oxidation is measured using an indirect calorimeter, which determines metabolic flexibility.
1 secondary outcome
Evaluating mitochondrial function through measurement of phosphocreatine (PCr) recovery by phosphorus magnetic resonance spectroscopy (31P-MRS) within the skeletal muscle
Time frame: 1.5 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2022.
- Derived from this study: PubMed 36413408Mancilla RF, Lindeboom L, Grevendonk L, Hoeks J, Koves TR, Muoio DM, Schrauwen P, Schrauwen-Hinderling V, Hesselink MK. Skeletal muscle mitochondrial inertia is associated with carnitine acetyltransferase activity and physical function in humans. JCI Insight. 2023 Jan 10;8(1):e163855. doi: 10.1172/jci.insight.163855.
- Derived from this study: PubMed 33258025Houzelle A, Jorgensen JA, Schaart G, Daemen S, van Polanen N, Fealy CE, Hesselink MKC, Schrauwen P, Hoeks J. Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity. Diabetologia. 2021 Feb;64(2):424-436. doi: 10.1007/s00125-020-05335-w. Epub 2020 Nov 30.
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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.
Patrick Schrauwen, PhD study director
Maastricht University
Lauren M Sparks, PhD principal investigator
Maastricht University
Madeleen Bosma, M.S. principal investigator
Maastricht University
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 Healthy and Obesity, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 19 Sep 2022. 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 Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Madeleen Bosma, M.S. (31433884254, m.bosma@maastrichtuniversity.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Euglycemic-hyperinsulinemic clamp for measurement of insulin sensitivity and metabolic flexibility (time frame: 10 hours). 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 NCT01298375, which also lists 2 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 19 Sep 2022.