Clinical trial NCT03541096: Winter-Swimming and Brown Adipose Tissue Activity in Middel-aged Obese Subjects (WinterBAT).
Official title: The Impact of Winter Swimming on Brown Adipose Tissue Recruitment and Metabolic Health in Middel-aged Obese Pre-diabetic Subjects.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Adipose Tissue, Brown
Brown Adipose Tissue
Uncoupling Protein 1
Cold Exposure
Obesity
Type 2 Diabetes Mellitus
Winter Swimming
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2018-05-30
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study investigates repetitive cold-water exposure on brown fat activity assessed by PET/CT scanning. Furthermore we will assess glucose control upon winter-swimming. Obese prediabetic men and women will be randomized to winter-swimming or control conditions for 4 months.

Detailed description: Brown fat (BAT) is an energy-consuming tissue. Long-term activation of BAT in adults increases clearance of blood glucose and non-esterified fatty acids (NEFA), insulin sensitivity and metabolic rate. Moreover, adipokines released from BAT, known as batokines, represent a promising but currently unexplored area in terms of metabolic regulation. Cooling activates BAT; however, current cooling protocols fail to activate BAT in a large part of the population. Whether this failure in activation is related to biology, inefficient detection or cooling protocols is unknown. With our initial acute cooling study (protocol number: H-16038581), these protocols have successfully been optimized whereupon novel batokines will be identified. Having established a methodology for assessing BAT activity and batokine profiles, a longer-term cooling intervention (winter swimming) will be performed to examine the effect of repetitive cold-water exposure on BAT activity. Obese pre-diabetic subjects will be included in a 4-month supervised winter swimming (WS) intervention.

It is hypothesized, that repetitive cold-water exposure constituted by WS, increase BAT activation and volume, followed by improved glycemic control in obese pre-diabetic subjects.

Method The study is a randomized controlled, parallel-group intervention study. The investigator will recruit 30 obese pre-diabetic non-winter-swimmers to participate in a WS intervention group (n=15) or control group (n=15) with no WS activities. Subjects will either be randomized to the WS group, who will winter-swim 4 months, 2-3 times/week including sauna-visits if desired, or control conditions with no WS during the 4 months (October to May).

Main aims

* To assess whether WS will have an immediate effect on BAT recruitment or function.
* To assess whether WS will have an effect on glycemic control.

Eligibility criteria: Inclusion Criteria:

* Waist circumference above 80 cm for women and 94 cm for men.
* BMI \> 25 but \<40 kg/m2
* Age \> 40 years.
* Low to moderate physical activity level (no physical activity or on average 30 minutes of moderate physical activity per day and not more than 3 hours of training pr. Week)

Subjects will be included in either one of these cases after the screening:

* Fasting plasma glucose above 5.6 millimol per liter (mmoL/L).
* HbA1C \>39 millimol per mol (mmol/mol).
* 2 hour plasma glucose after a 75 g. oral glucose tolerance test (OGTT) above 7.8 mmol/L.

Exclusion Criteria:

* Winter swimmer
* Any history of Cancer,
* Clinically significant liver, kidney, heart, inflammatory or lung-disease.
* Pregnancy
* Taking medication (not for hay fever), including glucose-lowering treatment.
* HbA1c \>55 mmol/mol and/or 2-h plasma glucose in the 75-g OGTT \> 15 mmol/L, fasting plasma glucose above 6.9.
* Iron deficiency
* Increased International Normalised Ratio for coagulation (INR).
* Femoral hernia, vene prostheses (pants prosthesis), thrombs in v. Femoralis.
* Abnormal ultrasound echocardiography of the heart found at the health-examination day.
* Contraindications to cold exposure including severe Raynauds disease.
* History of alcohol abuse or use of more than 14 units pr. Week.
* History of drug abuse, including marihuana.
* Smoking including occasional smoking.
* Pacemaker or other electronics implanted in the body.
* Claustrophobia, communication problems, including understanding the experimental protocol.
* History of contrast allergy.

Primary outcomes:
measure: Difference between groups in change in brown adipose tissue (BAT) activity during cooling
timeFrame: Day 0 (before intervention) and Day 120 (after intervention)
Secondary outcomes:
measure: Difference between groups in change in glycemic control
timeFrame: Day 0 (before intervention) and Day 120 (after intervention)
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Center for Inflammation and Metabolism/ Center for Physical Activity Research
Study officials:
affiliation: Rigshospitalet, Denmark
name: Camilla Schéele, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hanssen MJ, Hoeks J, Brans B, van der Lans AA, Schaart G, van den Driessche JJ, Jorgensen JA, Boekschoten MV, Hesselink MK, Havekes B, Kersten S, Mottaghy FM, van Marken Lichtenbelt WD, Schrauwen P. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nat Med. 2015 Aug;21(8):863-5. doi: 10.1038/nm.3891. Epub 2015 Jul 6.
citation: Hanssen MJ, van der Lans AA, Brans B, Hoeks J, Jardon KM, Schaart G, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD. Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans. Diabetes. 2016 May;65(5):1179-89. doi: 10.2337/db15-1372. Epub 2015 Dec 30.
citation: van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009 Apr 9;360(15):1500-8. doi: 10.1056/NEJMoa0808718.
citation: Lee P, Smith S, Linderman J, Courville AB, Brychta RJ, Dieckmann W, Werner CD, Chen KY, Celi FS. Temperature-acclimated brown adipose tissue modulates insulin sensitivity in humans. Diabetes. 2014 Nov;63(11):3686-98. doi: 10.2337/db14-0513. Epub 2014 Jun 22.
citation: Gibas-Dorna M, Checinska Z, Korek E, Kupsz J, Sowinska A, Krauss H. Cold Water Swimming Beneficially Modulates Insulin Sensitivity in Middle-Aged Individuals. J Aging Phys Act. 2016 Oct;24(4):547-554. doi: 10.1123/japa.2015-0222. Epub 2016 Aug 24.