The Effects of Weight Loss on Neuroadrenergic Function

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2013 by Baker Heart Research Institute
Sponsor:
Information provided by (Responsible Party):
Nora E. Straznicky, Baker Heart Research Institute
ClinicalTrials.gov Identifier:
NCT01771042
First received: January 15, 2013
Last updated: January 16, 2013
Last verified: January 2013
  Purpose

Elevated subconscious nervous system activity is a characteristic of the obese state and contributes importantly to the risk of heart disease and diabetes. This project will compare sympathetic nervous system activity and function in a group of obese persons with differing levels of sugar tolerance (normal, impaired and type 2 diabetic). Inter-relationships with insulin action, blood pressure, heart and kidney function will be determined before and after a 4-month weight loss and 3-month weight loss maintenance program.

It is hypothesized that the transition from normal sugar tolerance to impaired sugar tolerance to type 2 diabetes will be accompanied by escalating sympathetic nervous system dysfunction. Furthermore, that weight loss will favorably improve sympathetic function, with greatest benefits occurring in those subjects who are insulin resistant with high blood insulin concentration.


Condition Intervention
Obesity
Type 2 Diabetes
Metabolic Syndrome
Other: Dietary weight loss at 25% energy deficit

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Neuroadrenergic Dysfunction Along the Diabetes Continuum: Benefits of Weight Loss Within Different Strata of Metabolic Risk

Resource links provided by NLM:


Further study details as provided by Baker Heart Research Institute:

Primary Outcome Measures:
  • Change in whole-body norepinephrine kinetics [ Time Frame: 4 months and 7 months ] [ Designated as safety issue: No ]
    The study will examine the dynamic processes of norepinephrine spillover into and removal from the central plasma compartment using the isotope dilution technique.Measurements will be made at baseline, after 4 months active weight loss, and again after 3 months weight loss maintenance. The weight loss maintenance phase will permit differentiation of the effects of active weight loss (incorporating both negative energy balance and weight loss per se) and stable lower body weight on sympathetic neural parameters.


Secondary Outcome Measures:
  • Change in muscle sympathetic nerve activity [ Time Frame: 4 months and 7 months ] [ Designated as safety issue: No ]
    Muscle sympathetic nerve firing will be quantified by the technique of mirconeurography at baseline and after 4 months active weight loss and 3 months weight loss maintenance. The weight loss maintenance phase will permit differentiation of the effects of active weight loss (incorporating both negative energy balance and weight loss per se) and stable lower body weight on sympathetic nerve firing and pattern.


Other Outcome Measures:
  • Change in insulin sensitivity [ Time Frame: 4 months and 7 months ] [ Designated as safety issue: No ]
    Insulin sensitivity will be assessed by the gold standard euglycemic hyperinsulinemic clamp method at baseline and after 4 months active weight loss and 3 months weight loss maintenance. The weight loss maintenance phase will permit differentiation of the effects of active weight loss (incorporating both negative energy balance and weight loss per se) and stable lower body weight on insulin sensitivity.


Estimated Enrollment: 120
Study Start Date: April 2013
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Normal glucose tolerant

Weight loss attained by 25% caloric restriction.

This arm will be both a glycemic and time control. Initially they will undergo a 4-month weight maintenance phase (acting as time control), followed by 4 month weight loss.

Other: Dietary weight loss at 25% energy deficit
Dietary weight loss at 25% energy deficit. Dietary macronutrient content will comprise 25% protein, 30% fat and 45% carbohydrate.
Experimental: Impaired glucose tolerant

Weight loss using 25% caloric restriction.

Impaired glucose tolerant subjects will undergo 4 months weight loss (25% caloric deficit) followed by 3 months weight loss maintenance

Other: Dietary weight loss at 25% energy deficit
Dietary weight loss at 25% energy deficit. Dietary macronutrient content will comprise 25% protein, 30% fat and 45% carbohydrate.
Experimental: Type 2 diabetic hyperinsulinemic

Weight loss using 25% caloric restriction.

This group will undergo 4 months weight loss (25% caloric deficit) followed by 3 months weight loss maintenance

Other: Dietary weight loss at 25% energy deficit
Dietary weight loss at 25% energy deficit. Dietary macronutrient content will comprise 25% protein, 30% fat and 45% carbohydrate.
Experimental: Type 2 diabetic hypoinsulinemic

Weight loss via 25% caloric restriction.

This group will undergo 4 months weight loss (25% caloric deficit) followed by 3 months weight loss maintenance

Other: Dietary weight loss at 25% energy deficit
Dietary weight loss at 25% energy deficit. Dietary macronutrient content will comprise 25% protein, 30% fat and 45% carbohydrate.

Detailed Description:

The twin epidemics of obesity and diabetes represent a major public health problem worldwide. There is a growing body of evidence to suggest that autonomic dysfunction, comprising elevated sympathetic nervous system (SNS) activity and blunted sympathetic neural responsiveness plays a role in both the pathogenesis and target organ complications of obesity and diabetes. The proposed project will undertake a detailed comparative analysis of neuroadrenergic function along the diabetes continuum, its inter-relationship with insulin sensitivity and secretion, and target organ function, and the benefits of active weight loss and weight loss maintenance within different strata of metabolic risk.

  Eligibility

Ages Eligible for Study:   45 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Men and postmenopausal women (n=120), untreated, weight-stable, non-smoking, aged 45-65 years, BMI 27-45 kg/m2, will be recruited. Glucose tolerance status will be determined by a 75-g oral glucose tolerance test (OGTT), using WHO criteria (53): normal glucose tolerance, fasting plasma glucose < 7.0 mmol/L and 2-h plasma glucose < 7.8 mmol/L; IGT, fasting plasma glucose < 7.0 mmol/L and 2-h plasma glucose > 7.8 and < 11.1 mmol/L; T2D, fasting plasma glucose > 7.0 mmol/L or 2-h plasma glucose > 11.1 mmol/L. Hyper-insulinemia will be defined as an insulin area under the curve during OGTT > 8000 mU/L ∙ min-1 and hypo-insulinemia as < 8000 mU/L ∙ min-1.

Exclusion Criteria:

Prior history of cardiovascular disease (previous myocardial infarction, angina, stroke, heart failure, secondary hypertension), renal (serum creatinine >0.12 mmol/L or estimated GFR <60 ml/min/1.73 m2) or hepatic disease or diseases which may affect measured parameters (e.g. thyroid disease); severe hypertension; a history of surgical weight loss; CPAP therapy; and >4 alcoholic drinks/day. T2D individuals with moderate hyperglycemia (HbA1c >9%) will be excluded so that hypoglycaemic pharmacotherapy may be instituted (54). Participants will be sought through newspaper advertising and poster displays in primary health care centres (General Practices). Newly diagnosed T2D subjects

  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: NCT01771042

Contacts
Contact: Dr Nora E Straznicky, PhD MPH 61 3 8532 1371 nora.straznicky@bakeridi.edu.au
Contact: Ms Mariee T Grima, BNutr MDiet 61 3 8532 1523 mariee.grima@bakeridi.edu.au

Locations
Australia, Victoria
Baker IDI Heart & Diabetes Institute Not yet recruiting
Melbourne, Victoria, Australia, 8008
Contact: Nora E Straznicky, PhD MPH    61 3 8532 1371    nora.straznicky@bakeridi.edu.au   
Principal Investigator: Nora E Straznicky, PhD MPH         
Sponsors and Collaborators
Baker Heart Research Institute
Investigators
Principal Investigator: Dr Nora E Straznicky, PhD MPH Baker IDI Heart & Diabetes Institute
  More Information

No publications provided

Responsible Party: Nora E. Straznicky, Group Leader/Senior Research Officer, Baker Heart Research Institute
ClinicalTrials.gov Identifier: NCT01771042     History of Changes
Other Study ID Numbers: 1/13, 1/13
Study First Received: January 15, 2013
Last Updated: January 16, 2013
Health Authority: Bayside Health, Melbourne, Australia:

Keywords provided by Baker Heart Research Institute:
weight loss
metabolic syndrome
sympathetic nervous system
insulin resistance
glucose tolerance

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Obesity
Weight Loss
Metabolic Syndrome X
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Body Weight Changes
Insulin Resistance
Hyperinsulinism

ClinicalTrials.gov processed this record on August 26, 2014