Activating Brown Adipose Tissue Through Exercise (ACTIBATE)

February 10, 2015 updated by: Jonatan Ruiz Ruiz, Universidad de Granada

Activating Brown Adipose Tissue Through Exercise: Randomized Controlled Trial

The energy burning capacity of brown adipose tissue makes it an attractive target for anti-obesity therapies. Sympathetic nervous system (SNS) is the classical regulator of brown adipose tissue; however, recent findings show a pool of novel brown adipose tissue activators that sidestep the need for stimulating the SNS, including cardiac natriuretic peptides. Of interest is that both SNS and non-SNS brown adipose tissue activators are sensitive to physical exercise, which opens new horizons and opportunities to study the potential effect of exercise-based therapeutic interventions. Moreover, a new protein released by exercise-stimulated skeletal muscle, irisin, seems to play a key role in the browning program of white adipose tissue. Most of the available evidence comes from animal studies, which is sometimes difficult to infer to human physiology. The overall objective of the ACTIBATE randomized controlled trial is to study the effect of long-term exercise training (6 months) on brown adipose tissue activity and quantity (primary outcomes) in young overweight and obese adults. The clinical significance of activating and recruiting brown adipose tissue on resting metabolic rate and cardiometabolic profile in humans will be determined. The investigators will also study at the molecular level the benefits of exercise on the regulation pathways in two different tissues: white adipose tissue and skeletal muscle, as well as identifying possible cross-talk between the exercising muscle and heart, and fat. Information from exercise-induced signaling on brown adipose tissue, white adipose tissue and skeletal muscle will help on identifying potential molecular therapeutic candidates.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The energy burning capacity of brown adipose tissue (BAT) makes it an attractive target for antiobesity therapies. Sympathetic nervous system (SNS) is the classical regulator of BAT; however, recent findings show a pool of novel BAT activators that sidestep the need for stimulating the SNS. Of interest is that both SNS and non-SNS BAT activators are sensitive to physical exercise, which opens new horizons and opportunities to study the potential effect of exercise-based therapeutic interventions. Moreover, a new protein released by exercise-stimulated skeletal muscle, irisin, seems to play a key role in the browning program in white adipose tissue. Most of the available evidence comes from animal studies, which is sometimes difficult to infer to human physiology. To determine whether a controlled physical exercise program is able to facilitate BAT maintenance and function, stimulating pre-existing brown precursors and inducing the specific gene program to favor white-to-brown adipocyte transformation in humans is of clinical relevance.

The primary objective of the ACTIBATE randomized controlled trial (RCT) is to quantify the dose-effect of different exercise intensities, i.e. no exercise, moderate-intensity and vigorous-intensity, on BAT activity and mass (primary outcome), and on energy expenditure, thermogenic response to a test meal, shivering threshold, and cardiovascular disease risk factors, in young adults. The investigators will also obtain biopsies from white adipose tissue and skeletal muscle to analyse the expression of genes encoding proteins involved in the thermogenic machinery. The intervention groups will train 4-5 days/week (60 min per session) for a 24-week period.

With the final aim of making the exercise program transferable to society, the basis for the specific exercise dose in ACTIBATE is the physical activity recommendations for adults proposed by the World Health Organization. Since there is no information regarding the ideal exercise model to activate and recruit BAT, a major objective of ACTIBATE is to evaluate various exercise intensity levels that fall within the current public health recommendations to test whether higher intensity levels provides more benefit than the standard moderate-intensity level. ACTIBATE will combine both aerobic and resistance training.

Study Type

Interventional

Enrollment (Anticipated)

180

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jonatan R Ruiz, PhD
  • Phone Number: +34 958 242 754
  • Email: ruizj@ugr.es

Study Locations

  • Spain
      • Granada, Spain, 18011
        • Recruiting
        • University of Granada
        • Contact:
          • Jonatan R Ruiz, PhD
          • Phone Number: 0034958242754
          • Email: ruizj@ugr.es
        • Principal Investigator:
          • Jonatan Ruiz, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 25 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • BMI: 20-35 kg/m2.
  • Not engaged in regular physical activity >20 min on >3 days/week.
  • Not participating in a weight loss program.
  • Stable weight over the last 3 months (body weight changes <3 kg).
  • Normal electrocardiogram.
  • Participants must be capable and willing to provide consent, understand exclusion criteria and accept the randomized group assignment.

Exclusion Criteria:

  • History of cardiovascular disease.
  • Diabetes or hypertension.
  • Pregnancy, or planning to get pregnant during the study period.
  • Medication for hypertension, hyperlipidemia, hyperuricemia or other illness.
  • Beta blockers or benzodiazepins use.
  • Smoking.
  • Frequent exposure to cold temperatures (Granada is surrounded by high mountains where people can sky or do trekking).
  • Taking medication for thyroid.
  • Other significant medical conditions that are life-threatening or that can interfere with or be aggravated by exercise.
  • Unwillingness to either complete the study requirements or to be randomized into control or training group.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
NO_INTERVENTION: Usual care group (control)
Participants randomly assigned to the usual care (control) group will receive general advices from the exercise-training specialist about the positive effects of physical activity at the start of the study. The investigators will prepare informative pamphlets describing the benefits of physical activity that the investigators group has prepared for the Region of Andalucía (Southern Spain),http://www.juntadeandalucia.es/salud/servicios/contenidos/andaluciaessalud/docs/130/Guia_Recomendaciones_AF.pdf.
EXPERIMENTAL: Moderate-intensity group
Exercise training based on recommendations for adults (WHO)
Other: Exercise training based on recommendations for adults (WHO)
The length of the trial will be 6 months. the total time of aerobic exercise in both moderate-intensity and vigorous-intensity groups will be 150 minutes/week, whereas the time needed to complete the resistance training exercises will be ≈15-30 minutes for both groups.
EXPERIMENTAL: Vigorous-intensity group
Exercise training based on recommendations for adults (WHO)
Other: Exercise training based on recommendations for adults (WHO)
The length of the trial will be 6 months. the total time of aerobic exercise in both moderate-intensity and vigorous-intensity groups will be 150 minutes/week, whereas the time needed to complete the resistance training exercises will be ≈15-30 minutes for both groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from Baseline in BAT mass and activity evaluated with Positron emission tomography/computed tomography (PET/CT)
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in gene expression of white adipose tissue, aliquots will be obtained by biopsies.
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in gene expression of muscle, aliquots will be obtained by biopsies.
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Aliquots will be designated to gene expression, immunoblotting and morphologic studies.
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in resting energy expenditure measured through indirect calorimetry
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in meal Induced Thermogenesis measured through indirect calorimetry
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Cold Induced Thermogenesis measured through indirect calorimetry
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Body composition: fat mass. Using a Dual Energy X-ray Absorptiometry scan
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Body composition: lean body mass Using a Dual Energy X-ray Absorptiometry scan
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Shivering threshold: Temperature of water in a water perfuse vest connected to a chiller unit
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Thermic response to cold exposure with both subjective (Visual Analog Scales) and objective measures (skin and sublingual temperature)
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in subjective Thermic response to cold exposure: Visual Analog Scale
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Thermic response to a test meal with skin temperature
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Appetite: ad-libitum meal
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Appetite: Visual Analog Scale after a test meal
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Lipid Profile: In a blood sample
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in biomolecular markers: energy metabolism during cold exposure: In a blood sample
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Cardiorespiratory fitness measured on a maximum effort test
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Thermic response to a maximum effort test record with skin thermal receptors
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Muscular strength: 1 Repetition Maximum
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Dietary habits: 24h questionaire
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Physical activity levels: With an accelerometer
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)
Change from Baseline in Basal Heart Rate Variability: with a heart rate monitor
Time Frame: Baseline and 6 month later (immediately after the interventions ends)
Baseline and 6 month later (immediately after the interventions ends)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidad de Granada

Collaborators

Instituto de Salud Carlos III
Hospital Clinico Universitario San Cecilio
University Hospital Virgen de las Nieves

Investigators

  • Principal Investigator: Jonatan R Ruiz, PhD, Universidad de Granada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2015

Primary Completion (ANTICIPATED)

July 1, 2017

Study Completion (ANTICIPATED)

July 1, 2017

Study Registration Dates

First Submitted

February 3, 2015

First Submitted That Met QC Criteria

February 10, 2015

First Posted (ESTIMATE)

February 18, 2015

Study Record Updates

Last Update Posted (ESTIMATE)

February 18, 2015

Last Update Submitted That Met QC Criteria

February 10, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PI13/01393

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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