Brown Adipose Tissue Pilot

Aging Clinical Trial

— BATSP  

Official title:

BAT as a Therapeutic for the Metabolic and Cardiac Dysfunction With Senescence Pilot

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03793127
• Other study ID #: TRIMD 1344107
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 23, 2019
• Est. completion date: December 2023

Study information

• Verified date: July 2023
• Source: AdventHealth Translational Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this protocol is to develop a reliable method to determine BAT mass in young and older adults by magnetic resonance imaging.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: December 2023
• Est. primary completion date: May 13, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

• Capable of providing informed consent and has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board and provided Health Insurance Portability and Accountability Act authorization (HIPAA) or other privacy authorization prior to any participation in study.
• Adult female or male, 20-40 or 60-80 years of age, inclusive at time of screening.
• BMI =19.0 and =34.9 kg/m2, inclusive at time of screening.
• Stable weight (No gain/loss of = 10 lbs within 6 months prior to screening).
• Non-smokers as defined by not smoked any tobacco or nicotine-containing products vape pens or vaporizers within 3 months prior to screening.

Exclusion Criteria:

• History of type 1 or type 2 diabetes per self-report at screening visit 1; or Hgb A1c = 6.5% at screening..
• Actively pursuing weight loss and/or lifestyle changes at time of screening.
• Weight > 450 lbs at screening.
• Uncontrolled hypertension (BP >160 mmHg systolic or >100 mmHg diastolic).
• Mini Mental State Exam (MMSE) <21, only applicable for those 60-80 years of age
• Significant cardiovascular event (e.g. myocardial infarction, stroke) = 6 months prior to screening visit; or stated history of congestive heart failure; or evidence of cardiovascular disease assessed during the ECG at screening.
• Current infection (requiring prescription antimicrobial or antiviral medication, or hospitalization), or corticosteroid treatment (with the exception of inhaled or topical steroids) in the last 3 months prior to screening visit.
• Prescription strength anti-inflammatory medication in the 6 weeks prior to screening.
• Surgery requiring >2 days of hospitalization in the last 3 weeks prior to screening visit.
• Active malignancy or autoimmune disease.
• History of chronic, contagious, infectious disease, such as active tuberculosis, Hepatitis B or C, or HIV, per self-report.
• History of uncontrolled severe diarrhea, nausea or vomiting within 3 months of screening.
• Uncontrolled severe (including stage III or above) gastrointestinal absorption-related disorders, within 3 months of screening, such as: obstruction of the gastrointestinal tract, inflammatory bowel disease, short bowel syndrome, gastroesophageal reflux disease, gastroparesis, peptic ulcer disease, celiac disease, intestinal dysmotility, diverticulitis, ischemic colitis.
• History of drug or alcohol abuse (> 3 drinks per day) within the last 5 years.
• Pregnant, lactating or is within 6 weeks postpartum prior to the screening visit.
• Metal implants (pace-maker, aneurysm clips) based on Investigator's judgment at screening.
• Unable to participate in MRI assessments due to physical limitations of equipment tolerances (e.g. MRI bore size) based on Investigator's judgment at screening.
• Unable to tolerate MRI imaging or claustrophobia.
• Urine albumin-to-creatinine ratio (UACR) =300 mg/g in a single urine specimen (per National Kidney Foundation guideline) at screening.
• Impaired renal function: estimated glomerular filtration rate (eGFR) = 50 ml/min/1.73m2 determined at screening.
• Significantly impaired liver function in the opinion of the study PI (mild asymptomatic fatty liver is acceptable), or hepatic enzyme tests are =2.5 times normal limit at time of screening.
• Total cholesterol level is ?300 mg/dL at screening.
• Participant has inadequately treated hyperthyroidism (thyroid stimulating hormone [TSH] below normal range) or hypothyroidism (TSH>ULN (upper limit normal) to <10U/mL and symptomatic, or TSH >10 U/mL) at time of screening.

Related Conditions & MeSH terms

• Aging

Intervention

Other:
• Maximal oxygen consumption (V02 max)
Aerobic fitness will be determined by measuring V02 max during a stationary bicycle exercise test.
• Brown adipose tissue (BAT) imaging
Brown adipose tissue will be differentiated from white adipose tissue using fat fraction and T2* relaxation time maps generated from a commercially available modified 6-point Dixon (mDixon) water-fat separation method.
• Muscle function testing
This test will be done on a machine called a Biodex. We will measure the speed at which subjects move resistance at different percentages of their peak strength.

Locations

Country	Name	City	State
United States	Translational Research Institute for Metabolism and Diabetes	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AdventHealth Translational Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (19)

Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Weller H, Waurisch C, Eychmuller A, Gordts PL, Rinninger F, Bruegelmann K, Freund B, Nielsen P, Merkel M, Heeren J. Brown adipose tissue activity controls triglyceride clearance. Nat Med. 2011 Feb;17(2):200-5. doi: 10.1038/nm.2297. Epub 2011 Jan 23. — View Citation

Berbee JF, Boon MR, Khedoe PP, Bartelt A, Schlein C, Worthmann A, Kooijman S, Hoeke G, Mol IM, John C, Jung C, Vazirpanah N, Brouwers LP, Gordts PL, Esko JD, Hiemstra PS, Havekes LM, Scheja L, Heeren J, Rensen PC. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development. Nat Commun. 2015 Mar 10;6:6356. doi: 10.1038/ncomms7356. — View Citation

Costantino S, Paneni F, Cosentino F. Ageing, metabolism and cardiovascular disease. J Physiol. 2016 Apr 15;594(8):2061-73. doi: 10.1113/JP270538. Epub 2015 Oct 22. — View Citation

Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009 Apr 9;360(15):1509-17. doi: 10.1056/NEJMoa0810780. — View Citation

Dulloo AG, Miller DS. Energy balance following sympathetic denervation of brown adipose tissue. Can J Physiol Pharmacol. 1984 Feb;62(2):235-40. doi: 10.1139/y84-035. — View Citation

Graja A, Schulz TJ. Mechanisms of aging-related impairment of brown adipocyte development and function. Gerontology. 2015;61(3):211-7. doi: 10.1159/000366557. Epub 2014 Dec 20. — View Citation

Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP. Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest. 1998 Jul 15;102(2):412-20. doi: 10.1172/JCI3155. — View Citation

Gunawardana SC, Piston DW. Reversal of type 1 diabetes in mice by brown adipose tissue transplant. Diabetes. 2012 Mar;61(3):674-82. doi: 10.2337/db11-0510. Epub 2012 Feb 7. — View Citation

Kalyani RR, Egan JM. Diabetes and altered glucose metabolism with aging. Endocrinol Metab Clin North Am. 2013 Jun;42(2):333-47. doi: 10.1016/j.ecl.2013.02.010. Epub 2013 Mar 22. — View Citation

Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, Asumi M, Sugawara A, Totsuka K, Shimano H, Ohashi Y, Yamada N, Sone H. Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA. 2009 May 20;301(19):2024-35. doi: 10.1001/jama.2009.681. — View Citation

Lowell BB, S-Susulic V, Hamann A, Lawitts JA, Himms-Hagen J, Boyer BB, Kozak LP, Flier JS. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature. 1993 Dec 23-30;366(6457):740-2. doi: 10.1038/366740a0. — View Citation

Lynes MD, Leiria LO, Lundh M, Bartelt A, Shamsi F, Huang TL, Takahashi H, Hirshman MF, Schlein C, Lee A, Baer LA, May FJ, Gao F, Narain NR, Chen EY, Kiebish MA, Cypess AM, Bluher M, Goodyear LJ, Hotamisligil GS, Stanford KI, Tseng YH. The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue. Nat Med. 2017 May;23(5):631-637. doi: 10.1038/nm.4297. Epub 2017 Mar 27. Erratum In: Nat Med. 2017 Nov 7;23 (11):1384. — View Citation

Rothwell NJ, Stock MJ. Effects of age on diet-induced thermogenesis and brown adipose tissue metabolism in the rat. Int J Obes. 1983;7(6):583-9. — View Citation

Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009 Jul;58(7):1526-31. doi: 10.2337/db09-0530. Epub 2009 Apr 28. — View Citation

Stanford KI, Lynes MD, Takahashi H, Baer LA, Arts PJ, May FJ, Lehnig AC, Middelbeek RJW, Richard JJ, So K, Chen EY, Gao F, Narain NR, Distefano G, Shettigar VK, Hirshman MF, Ziolo MT, Kiebish MA, Tseng YH, Coen PM, Goodyear LJ. 12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake. Cell Metab. 2018 May 1;27(5):1111-1120.e3. doi: 10.1016/j.cmet.2018.03.020. Erratum In: Cell Metab. 2018 Jun 5;27(6):1357. — View Citation

Stanford KI, Middelbeek RJ, Townsend KL, An D, Nygaard EB, Hitchcox KM, Markan KR, Nakano K, Hirshman MF, Tseng YH, Goodyear LJ. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest. 2013 Jan;123(1):215-23. doi: 10.1172/JCI62308. Epub 2012 Dec 10. — View Citation

Thoonen R, Ernande L, Cheng J, Nagasaka Y, Yao V, Miranda-Bezerra A, Chen C, Chao W, Panagia M, Sosnovik DE, Puppala D, Armoundas AA, Hindle A, Bloch KD, Buys ES, Scherrer-Crosbie M. Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy. J Mol Cell Cardiol. 2015 Jul;84:202-11. doi: 10.1016/j.yjmcc.2015.05.002. Epub 2015 May 9. — View 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. Erratum In: N Engl J Med. 2009 Apr 30;360(18):1917. — View Citation

Yazdanyar A, Newman AB. The burden of cardiovascular disease in the elderly: morbidity, mortality, and costs. Clin Geriatr Med. 2009 Nov;25(4):563-77, vii. doi: 10.1016/j.cger.2009.07.007. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Collection of imaging of BAT by magnetic resonance imaging from 10 participants in each of young and old study groups.	Brown adipose tissue will be differentiated from white adipose tissue using fat fraction and T2* relaxation time maps generated from a commercially available modified 6-point Dixon (mDixon) water-fat separation method. The participant may be removed from the magnet and repositioned during the exam in order to determine the same day variability of this method.	30 minutes

External Links

•   Translational Research Institute for Metabolism and Diabetes