Metabolic Phenotyping in Humans (MetPhe)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by Maastricht University Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01298375
First received: February 16, 2011
Last updated: July 18, 2012
Last verified: July 2012
  Purpose

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.


Condition
Healthy
Obesity
Type 2 Diabetes Mellitus

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Metabolic Characterization of Type 2 Diabetic, Obese, Lean Sedentary and Endurance Trained Individuals in Vivo, ex Vivo and in Vitro

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • Euglycemic-hyperinsulinemic clamp for measurement of insulin sensitivity and metabolic flexibility [ Time Frame: 10 hours ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Biospecimen Retention:   Samples With DNA

DNA, RNA, tissue, primary myoblasts, mitochondria


Estimated Enrollment: 132
Study Start Date: March 2011
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
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:

  1. assess metabolic flexibility as measured by a euglycemic-hyperinsulinemic clamp
  2. measure in vivo mitochondrial function by MRS of phosphocreatine (PCr) recovery
  3. 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
  4. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Human volunteers from the surrounding area

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01298375

Contacts
Contact: Madeleen Bosma, M.S. 31433884254 m.bosma@maastrichtuniversity.nl
Contact: Bram Brouwers, B.S. 31433884258 b.brouwers@maastrichtuniversity.nl

Locations
Netherlands
Maastricht University Recruiting
Maastricht, Limburg, Netherlands, 6200MD
Contact: Madeleen Bosma, M.S.    31433884254    m.bosma@maastrichtuniversity.nl   
Principal Investigator: Lauren M Sparks, PhD         
Principal Investigator: Madeleen Bosma, M.S.         
Sub-Investigator: Vera Schrauwen-Hindeling, PhD         
Sponsors and Collaborators
Maastricht University Medical Center
Investigators
Study Director: Patrick Schrauwen, PhD Maastricht University
Principal Investigator: Lauren M Sparks, PhD Maastricht University
Principal Investigator: Madeleen Bosma, M.S. Maastricht University
  More Information

No publications provided

Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01298375     History of Changes
Other Study ID Numbers: NL35178.068.11
Study First Received: February 16, 2011
Last Updated: July 18, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:
Metabolic flexibility
Mitochondrial function
Human primary myoblasts
Lipid metabolism

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Obesity
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on August 21, 2014