Activating Brown Adipose Tissue Through Exercise

NCT ID: NCT02365129

Last Updated: 2015-02-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-02-28

Study Completion Date

2017-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Obesity Diabetes Mellitus Metabolic Syndrome X

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Moderate-intensity group

Exercise training based on recommendations for adults (WHO)

Group Type EXPERIMENTAL

Exercise training based on recommendations for adults (WHO)

Intervention Type OTHER

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.

Vigorous-intensity group

Exercise training based on recommendations for adults (WHO)

Group Type EXPERIMENTAL

Exercise training based on recommendations for adults (WHO)

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type OTHER

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role collaborator

Hospital Clinico Universitario San Cecilio

OTHER

Sponsor Role collaborator

University Hospital Virgen de las Nieves

OTHER

Sponsor Role collaborator

Universidad de Granada

OTHER

Sponsor Role lead

Responsible Party

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Jonatan Ruiz Ruiz

Researcher

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jonatan R Ruiz, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidad de Granada

Locations

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University of Granada

Granada, Granada, Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Jonatan R Ruiz, PhD

Role: CONTACT

+34 958 242 754

Facility Contacts

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Jonatan R Ruiz, PhD

Role: primary

0034958242754

References

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Martin-Olmedo JJ, Jurado-Fasoli L, Osuna-Prieto FJ, Garcia-Fontana C, Garcia-Fontana B, Gracia-Marco L, Munoz-Torres M, Ruiz JR. Impact of 24-week concurrent training on bone parameters and plasma levels of osteoglycin and sclerostin in young, sedentary adults: secondary analyses from the ACTIBATE randomized controlled trial. Eur J Endocrinol. 2025 Apr 30;192(5):558-567. doi: 10.1093/ejendo/lvaf087.

Reference Type DERIVED
PMID: 40298018 (View on PubMed)

Martinez-Tellez B, Xu H, Ortiz-Alvarez L, Rodriguez-Garcia C, Schonke M, Jurado-Fasoli L, Osuna-Prieto FJ, Alcantara JMA, Acosta FM, Amaro-Gahete FJ, Folkerts G, Vilchez-Vargas R, Link A, Plaza-Diaz J, Gil A, Labayen I, Fernandez-Veledo S, Rensen PCN, Ruiz JR. Effect of a 24-week supervised concurrent exercise intervention on fecal microbiota diversity and composition in young sedentary adults: The ACTIBATE randomized controlled trial. Clin Nutr. 2025 Jun;49:128-137. doi: 10.1016/j.clnu.2025.04.008. Epub 2025 Apr 15.

Reference Type DERIVED
PMID: 40279809 (View on PubMed)

Amaro-Gahete FJ, Espuch-Oliver A, Cano-Nieto A, Alcantara JMA, Garcia-Lario JV, De Haro T, Llamas-Elvira JM, Munoz Torres M, Castillo MJ, Labayen I, Ruiz JR. Impact of 24-week supervised concurrent exercise on S-Klotho and vitamin D levels: A randomized controlled trial. J Sports Sci. 2024 Dec;42(24):2562-2571. doi: 10.1080/02640414.2025.2453328. Epub 2025 Jan 20.

Reference Type DERIVED
PMID: 39831661 (View on PubMed)

Alcantara JMA, Gonzalez-Acedo A, Amaro-Gahete FJ, Plaza-Florido A. Heart Rate and Its Variability Are Associated With Resting Metabolic Rate and Substrate Oxidation in Young Women but Not in Men. Am J Hum Biol. 2024 Nov;36(11):e24157. doi: 10.1002/ajhb.24157. Epub 2024 Sep 20.

Reference Type DERIVED
PMID: 39300911 (View on PubMed)

Dote-Montero M, Acosta FM, Sanchez-Delgado G, Merchan-Ramirez E, Amaro-Gahete FJ, Labayen I, Ruiz JR. Association of meal timing with body composition and cardiometabolic risk factors in young adults. Eur J Nutr. 2023 Aug;62(5):2303-2315. doi: 10.1007/s00394-023-03141-9. Epub 2023 Apr 26.

Reference Type DERIVED
PMID: 37100891 (View on PubMed)

Jurado-Fasoli L, Di X, Sanchez-Delgado G, Yang W, Osuna-Prieto FJ, Ortiz-Alvarez L, Krekels E, Harms AC, Hankemeier T, Schonke M, Aguilera CM, Llamas-Elvira JM, Kohler I, Rensen PCN, Ruiz JR, Martinez-Tellez B. Acute and long-term exercise differently modulate plasma levels of oxylipins, endocannabinoids, and their analogues in young sedentary adults: A sub-study and secondary analyses from the ACTIBATE randomized controlled-trial. EBioMedicine. 2022 Nov;85:104313. doi: 10.1016/j.ebiom.2022.104313. Epub 2022 Oct 27.

Reference Type DERIVED
PMID: 36374769 (View on PubMed)

Ortiz-Alvarez L, Acosta FM, Xu H, Sanchez-Delgado G, Vilchez-Vargas R, Link A, Plaza-Diaz J, Llamas JM, Gil A, Labayen I, Rensen PCN, Ruiz JR, Martinez-Tellez B. Fecal microbiota composition is related to brown adipose tissue 18F-fluorodeoxyglucose uptake in young adults. J Endocrinol Invest. 2023 Mar;46(3):567-576. doi: 10.1007/s40618-022-01936-x. Epub 2022 Oct 15.

Reference Type DERIVED
PMID: 36242744 (View on PubMed)

Martinez-Tellez B, Sanchez-Delgado G, Acosta FM, Alcantara JMA, Amaro-Gahete FJ, Martinez-Avila WD, Merchan-Ramirez E, Munoz-Hernandez V, Osuna-Prieto FJ, Jurado-Fasoli L, Xu H, Ortiz-Alvarez L, Arias-Tellez MJ, Mendez-Gutierrez A, Labayen I, Ortega FB, Schonke M, Rensen PCN, Aguilera CM, Llamas-Elvira JM, Gil A, Ruiz JR. No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial. Nat Commun. 2022 Sep 12;13(1):5259. doi: 10.1038/s41467-022-32502-x.

Reference Type DERIVED
PMID: 36097264 (View on PubMed)

Merchan-Ramirez E, Sanchez-Delgado G, Arrizabalaga-Arriazu C, Acosta FM, Arias-Tellez MJ, Munoz-Torres M, Garcia-Lario JV, Llamas-Elvira JM, Ruiz JR. Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults. J Physiol Biochem. 2022 Aug;78(3):629-640. doi: 10.1007/s13105-022-00881-w. Epub 2022 Apr 6.

Reference Type DERIVED
PMID: 35381950 (View on PubMed)

Mendez-Gutierrez A, Aguilera CM, Osuna-Prieto FJ, Martinez-Tellez B, Rico Prados MC, Acosta FM, Llamas-Elvira JM, Ruiz JR, Sanchez-Delgado G. Exercise-induced changes on exerkines that might influence brown adipose tissue metabolism in young sedentary adults. Eur J Sport Sci. 2023 Apr;23(4):625-636. doi: 10.1080/17461391.2022.2040597. Epub 2022 Apr 25.

Reference Type DERIVED
PMID: 35152857 (View on PubMed)

Acosta FM, Sanchez-Delgado G, Martinez-Tellez B, Alcantara JMA, Llamas-Elvira JM, Ruiz JR. Diurnal variations of cold-induced thermogenesis in young, healthy adults: A randomized crossover trial. Clin Nutr. 2021 Oct;40(10):5311-5321. doi: 10.1016/j.clnu.2021.08.010. Epub 2021 Aug 24.

Reference Type DERIVED
PMID: 34536639 (View on PubMed)

Jurado-Fasoli L, Amaro-Gahete FJ, Merchan-Ramirez E, Labayen I, Ruiz JR. Relationships between diet and basal fat oxidation and maximal fat oxidation during exercise in sedentary adults. Nutr Metab Cardiovasc Dis. 2021 Apr 9;31(4):1087-1101. doi: 10.1016/j.numecd.2020.11.021. Epub 2020 Dec 1.

Reference Type DERIVED
PMID: 33549436 (View on PubMed)

Sanchez-Delgado G, Alcantara JMA, Acosta FM, Martinez-Tellez B, Amaro-Gahete FJ, Merchan-Ramirez E, Lof M, Labayen I, Ravussin E, Ruiz JR. Energy Expenditure and Macronutrient Oxidation in Response to an Individualized Nonshivering Cooling Protocol. Obesity (Silver Spring). 2020 Nov;28(11):2175-2183. doi: 10.1002/oby.22972. Epub 2020 Sep 27.

Reference Type DERIVED
PMID: 32985119 (View on PubMed)

Sanchez-Delgado G, Acosta FM, Martinez-Tellez B, Finlayson G, Gibbons C, Labayen I, Llamas-Elvira JM, Gil A, Blundell JE, Ruiz JR. Brown adipose tissue volume and 18F-fluorodeoxyglucose uptake are not associated with energy intake in young human adults. Am J Clin Nutr. 2020 Feb 1;111(2):329-339. doi: 10.1093/ajcn/nqz300.

Reference Type DERIVED
PMID: 31826235 (View on PubMed)

Acosta FM, Sanchez-Delgado G, Martinez-Tellez B, Migueles JH, Amaro-Gahete FJ, Rensen PCN, Llamas-Elvira JM, Blondin DP, Ruiz JR. Sleep duration and quality are not associated with brown adipose tissue volume or activity-as determined by 18F-FDG uptake, in young, sedentary adults. Sleep. 2019 Dec 24;42(12):zsz177. doi: 10.1093/sleep/zsz177.

Reference Type DERIVED
PMID: 31555815 (View on PubMed)

Amaro-Gahete FJ, Sanchez-Delgado G, Ara I, R Ruiz J. Cardiorespiratory Fitness May Influence Metabolic Inflexibility During Exercise in Obese Persons. J Clin Endocrinol Metab. 2019 Dec 1;104(12):5780-5790. doi: 10.1210/jc.2019-01225.

Reference Type DERIVED
PMID: 31322652 (View on PubMed)

Acosta FM, Martinez-Tellez B, Sanchez-Delgado G, Migueles JH, Contreras-Gomez MA, Martinez-Avila WD, Merchan-Ramirez E, Alcantara JMA, Amaro-Gahete FJ, Llamas-Elvira JM, Ruiz JR. Association of Objectively Measured Physical Activity With Brown Adipose Tissue Volume and Activity in Young Adults. J Clin Endocrinol Metab. 2019 Feb 1;104(2):223-233. doi: 10.1210/jc.2018-01312.

Reference Type DERIVED
PMID: 30137350 (View on PubMed)

Sanchez-Delgado G, Martinez-Tellez B, Olza J, Aguilera CM, Labayen I, Ortega FB, Chillon P, Fernandez-Reguera C, Alcantara JMA, Martinez-Avila WD, Munoz-Hernandez V, Acosta FM, Prados-Ruiz J, Amaro-Gahete FJ, Hidalgo-Garcia L, Rodriguez L, Ruiz YA, Ramirez-Navarro A, Muros-de Fuentes MA, Garcia-Rivero Y, Sanchez-Sanchez R, de Dios Beas Jimenez J, de Teresa C, Navarrete S, Lozano R, Brea-Gomez E, Rubio-Lopez J, Ruiz MR, Cano-Nieto A, Llamas-Elvira JM, Jimenez Rios JA, Gil A, Ruiz JR. Activating brown adipose tissue through exercise (ACTIBATE) in young adults: Rationale, design and methodology. Contemp Clin Trials. 2015 Nov;45(Pt B):416-425. doi: 10.1016/j.cct.2015.11.004. Epub 2015 Nov 3.

Reference Type DERIVED
PMID: 26546068 (View on PubMed)

Other Identifiers

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PI13/01393

Identifier Type: -

Identifier Source: org_study_id

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