NCT02777138

Brief Summary

The accumulation and dysfunction of excess adipose (fat) tissue that occurs with ageing is associated with a number of chronic inflammatory disorders such as type 2 diabetes and cardiovascular disease but the underlying mechanisms are not understood.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
24

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started May 2016

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2016

Completed
5 days until next milestone

First Submitted

Initial submission to the registry

May 6, 2016

Completed
13 days until next milestone

First Posted

Study publicly available on registry

May 19, 2016

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2018

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2018

Completed
Last Updated

August 24, 2018

Status Verified

August 1, 2018

Enrollment Period

1.8 years

First QC Date

May 6, 2016

Last Update Submit

August 22, 2018

Conditions

Keywords

Adipose tissueInflammationAge ComparisonMacrophagesT-lymphocytesAdipose Progenitors

Outcome Measures

Primary Outcomes (1)

  • Differences in immune cell populations (macrophages/Tcells) in adipose tissue of young versus old males

    through to study completion, an average of 14 months

Secondary Outcomes (5)

  • the impact of ageing on mRNA expression of key metabolic and inflammatory genes in adipose tissue.

    through to study completion, an average of 14 months

  • the impact of ageing on metabolic and inflammatory protein secretions (into culture media) from adipose tissue

    through to study completion, an average of 14 months

  • differences in immune cell populations in muscle tissue and blood compared to adipose tissue from the same individuals and the impact of ageing on immune cell populations in muscle tissue.

    through to study completion, an average of 14 months

  • the impact of ageing on mRNA expression of other key metabolic and inflammatory genes in muscle tissue.

    through to study completion, an average of 14 months

  • activation/inhibition of e.g. insulin stimulated pathways in adipose and muscle tissues (for example assessment of Akt/IRS1 phosphorylation by western blot analysis).

    through to study completion, an average of 14 months

Study Arms (2)

Young males aged 20-35 years old

Maintaining a normal daily living lifestyle * Healthy * Reasonably active- PAL: 1.4-1.9 * Non-obese- Fat mass index based on DEXA of 4-8kg/m2 * Weight stable for more than 3 months (±3% body mass) * Non-smoker * No chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, peripheral arterial disease, insulin- or non-insulin dependent diabetes or other metabolic disorders * No daily consumption of analgesic or anti-inflammatory drug(s) including NSAIDs and corticosteroids, prescription or non-prescription * No medications that may influence lipid or carbohydrate metabolism or immune system function * No known negative reaction to lidocaine * No participation in heavy resistance training

Other: Maintaining a normal daily living lifestyle

Old males aged 65-85 years old

Maintaining a normal daily living lifestyle * Healthy * Reasonably active- PAL: 1.4-1.9 * Non-obese- Fat mass index based on DEXA of 4-8kg/m2 * Weight stable for more than 3 months (±3% body mass) * Non-smoker * No chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, peripheral arterial disease, insulin- or non-insulin dependent diabetes or other metabolic disorders * No daily consumption of analgesic or anti-inflammatory drug(s) including NSAIDs and corticosteroids, prescription or non-prescription * No medications that may influence lipid or carbohydrate metabolism or immune system function * No known negative reaction to lidocaine * No participation in heavy resistance training

Other: Maintaining a normal daily living lifestyle

Interventions

participants will undertake a normal lifestyle with no alterations to daily living in order to access the differences in tissue (muscle and adipose) and systemic inflammation between the two age cohorts

Old males aged 65-85 years oldYoung males aged 20-35 years old

Eligibility Criteria

Age20 Years - 85 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

general free-living public in the Bath and the surrounding areas

You may qualify if:

  • Male
  • Aged between 20-35 years (Group 1) or 65-85 years (Group 2)
  • Fat mass index based on DEXA between 4-8 kg/m2
  • Weight stable for more than 3 months (no change in weight +/- 3%)
  • Physical Activity Level (PAL) between 1.4 and 1.9
  • Non-smoker
  • Healthy

You may not qualify if:

  • Any chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, peripheral arterial disease, insulin- or non-insulin dependent diabetes or other metabolic disorders
  • Individuals who consume on a daily basis any analgesic or anti-inflammatory drug(s) including NSAIDs and corticosteroids, prescription or non-prescription
  • Taking any medications that may influence lipid or carbohydrate metabolism or immune system function
  • Individuals with a known negative reaction to lidocaine anaesthetic
  • Participation in heavy resistance training

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

university of bath - Department for Health

Bath, Somerset, BA2 7AY, United Kingdom

Location

Related Publications (20)

  • Alderete TL, Sattler FR, Sheng X, Tucci J, Mittelman SD, Grant EG, Goran MI. A novel biopsy method to increase yield of subcutaneous abdominal adipose tissue. Int J Obes (Lond). 2015 Jan;39(1):183-6. doi: 10.1038/ijo.2014.90. Epub 2014 May 21.

    PMID: 24849392BACKGROUND
  • Bourlier V, Zakaroff-Girard A, Miranville A, De Barros S, Maumus M, Sengenes C, Galitzky J, Lafontan M, Karpe F, Frayn KN, Bouloumie A. Remodeling phenotype of human subcutaneous adipose tissue macrophages. Circulation. 2008 Feb 12;117(6):806-15. doi: 10.1161/CIRCULATIONAHA.107.724096. Epub 2008 Jan 28.

    PMID: 18227385BACKGROUND
  • Cancello R, Tordjman J, Poitou C, Guilhem G, Bouillot JL, Hugol D, Coussieu C, Basdevant A, Bar Hen A, Bedossa P, Guerre-Millo M, Clement K. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes. 2006 Jun;55(6):1554-61. doi: 10.2337/db06-0133.

    PMID: 16731817BACKGROUND
  • Clement K, Viguerie N, Poitou C, Carette C, Pelloux V, Curat CA, Sicard A, Rome S, Benis A, Zucker JD, Vidal H, Laville M, Barsh GS, Basdevant A, Stich V, Cancello R, Langin D. Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. FASEB J. 2004 Nov;18(14):1657-69. doi: 10.1096/fj.04-2204com.

    PMID: 15522911BACKGROUND
  • Curat CA, Miranville A, Sengenes C, Diehl M, Tonus C, Busse R, Bouloumie A. From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. Diabetes. 2004 May;53(5):1285-92. doi: 10.2337/diabetes.53.5.1285.

    PMID: 15111498BACKGROUND
  • Dyck DJ, Heigenhauser GJ, Bruce CR. The role of adipokines as regulators of skeletal muscle fatty acid metabolism and insulin sensitivity. Acta Physiol (Oxf). 2006 Jan;186(1):5-16. doi: 10.1111/j.1748-1716.2005.01502.x.

    PMID: 16497175BACKGROUND
  • Fabbrini E, Cella M, McCartney SA, Fuchs A, Abumrad NA, Pietka TA, Chen Z, Finck BN, Han DH, Magkos F, Conte C, Bradley D, Fraterrigo G, Eagon JC, Patterson BW, Colonna M, Klein S. Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals. Gastroenterology. 2013 Aug;145(2):366-74.e1-3. doi: 10.1053/j.gastro.2013.04.010. Epub 2013 Apr 15.

    PMID: 23597726BACKGROUND
  • Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005 May;115(5):911-9; quiz 920. doi: 10.1016/j.jaci.2005.02.023.

    PMID: 15867843BACKGROUND
  • Goossens GH, Blaak EE, Theunissen R, Duijvestijn AM, Clement K, Tervaert JW, Thewissen MM. Expression of NLRP3 inflammasome and T cell population markers in adipose tissue are associated with insulin resistance and impaired glucose metabolism in humans. Mol Immunol. 2012 Mar;50(3):142-9. doi: 10.1016/j.molimm.2012.01.005. Epub 2012 Feb 8.

    PMID: 22325453BACKGROUND
  • Lumeng CN, Liu J, Geletka L, Delaney C, Delproposto J, Desai A, Oatmen K, Martinez-Santibanez G, Julius A, Garg S, Yung RL. Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue. J Immunol. 2011 Dec 15;187(12):6208-16. doi: 10.4049/jimmunol.1102188. Epub 2011 Nov 9.

    PMID: 22075699BACKGROUND
  • Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009 Aug;15(8):914-20. doi: 10.1038/nm.1964. Epub 2009 Jul 26.

    PMID: 19633658BACKGROUND
  • Ortega Martinez de Victoria E, Xu X, Koska J, Francisco AM, Scalise M, Ferrante AW Jr, Krakoff J. Macrophage content in subcutaneous adipose tissue: associations with adiposity, age, inflammatory markers, and whole-body insulin action in healthy Pima Indians. Diabetes. 2009 Feb;58(2):385-93. doi: 10.2337/db08-0536. Epub 2008 Nov 13.

    PMID: 19008342BACKGROUND
  • Pararasa C, Bailey CJ, Griffiths HR. Ageing, adipose tissue, fatty acids and inflammation. Biogerontology. 2015 Apr;16(2):235-48. doi: 10.1007/s10522-014-9536-x. Epub 2014 Nov 4.

    PMID: 25367746BACKGROUND
  • Thompson D, Karpe F, Lafontan M, Frayn K. Physical activity and exercise in the regulation of human adipose tissue physiology. Physiol Rev. 2012 Jan;92(1):157-91. doi: 10.1152/physrev.00012.2011.

    PMID: 22298655BACKGROUND
  • Travers RL, Motta AC, Betts JA, Bouloumie A, Thompson D. The impact of adiposity on adipose tissue-resident lymphocyte activation in humans. Int J Obes (Lond). 2015 May;39(5):762-9. doi: 10.1038/ijo.2014.195. Epub 2014 Nov 12.

    PMID: 25388403BACKGROUND
  • Trayhurn P, Drevon CA, Eckel J. Secreted proteins from adipose tissue and skeletal muscle - adipokines, myokines and adipose/muscle cross-talk. Arch Physiol Biochem. 2011 May;117(2):47-56. doi: 10.3109/13813455.2010.535835. Epub 2010 Dec 15.

    PMID: 21158485BACKGROUND
  • Varma V, Yao-Borengasser A, Rasouli N, Nolen GT, Phanavanh B, Starks T, Gurley C, Simpson P, McGehee RE Jr, Kern PA, Peterson CA. Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action. Am J Physiol Endocrinol Metab. 2009 Jun;296(6):E1300-10. doi: 10.1152/ajpendo.90885.2008. Epub 2009 Mar 31.

    PMID: 19336660BACKGROUND
  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003 Dec;112(12):1796-808. doi: 10.1172/JCI19246.

    PMID: 14679176BACKGROUND
  • Zeyda M, Farmer D, Todoric J, Aszmann O, Speiser M, Gyori G, Zlabinger GJ, Stulnig TM. Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes (Lond). 2007 Sep;31(9):1420-8. doi: 10.1038/sj.ijo.0803632. Epub 2007 Jun 26.

    PMID: 17593905BACKGROUND
  • Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003 Dec;112(12):1821-30. doi: 10.1172/JCI19451.

    PMID: 14679177BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

muscle and adipose biopsies blood plasma blood serum peripheral blood mononuclear cells

MeSH Terms

Conditions

Inflammation

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Dylan Thompson, Professor

    University of Bath

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Ph.D. Student

Study Record Dates

First Submitted

May 6, 2016

First Posted

May 19, 2016

Study Start

May 1, 2016

Primary Completion

March 1, 2018

Study Completion

October 1, 2018

Last Updated

August 24, 2018

Record last verified: 2018-08

Data Sharing

IPD Sharing
Will share

Locations