Fibrosis a New Pathological Actor in Adipose Tissue

NCT ID: NCT01655017

Last Updated: 2020-11-13

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

COMPLETED

Clinical Phase

NA

Total Enrollment

281 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-08

Study Completion Date

2018-04-06

Brief Summary

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Adipose tissue (AT) has specific alterations in obesity in particular increased fibrosis amount compared to lean subjects. Fibrosis amount measured by immunohistochemistry on adipose biopsies appears to to predict weight loss response after a bariatric surgery. Non invasive tools to measure fibrosis needs to be validated. The investigators primary aim is to validate a new device able to measure adipose tissue stiffness.

Thus the investigators plan to compare the stiffness results obtained with the device to the quantification of fibrosis using immuno-chemistry in massively obese patient's candidates to a bariatric surgery.

Detailed Description

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Adipose tissue (AT) has specific alterations in obesity that could link obesity to its comorbidities. In particular increased fibrosis abundance in AT has been observed in obese compared to lean subjects. The investigators previously observed that the amount of fibrosis in AT measured at baseline could predict surgery-induced weight loss. Patient with the higher amount of fibrosis at baseline were those who lost less fat mass one year after surgery.

To date fibrosis can only be measured using by immunohistochemistry after surgical biopsy. To that prospect, non invasive tools need to be validated, in particular device able to measure adipose tissue stiffness. The investigators hypothesis is that this new device is as powerful as IHC-quantified fibrosis to predict surgery induced weight loss.

To answer that question the investigators will evaluate adipose tissue stiffness with the device as well as quantify fibrosis using immuno-chemistry on AT biopsy in morbidly obese patients before and during the first year after a bariatric surgery.

The first objective is to validate the investigators new device by comparing both invasive fibrosis measurement on adipose tissue and non invasive stiffness measure The investigators second objective is to assess whether the investigators device can predict weight loss repose after bariatric surgery.

This project is based on a clinical protocol performed in massively obese subjects (BMI\>40 kg/m² or BMI\>35kg/m² with comorbidities). The investigators will recruit 250 obese patients addressed for bariatric surgery (bypass, sleeve or gastric banding). Clinical phenotype, biochemical analysis, body composition, systemic inflammation, adipose tissue biopsy (to evaluate inflammation and fibrosis) will be assessed at baseline and 3 and 12 months after surgery. Also at baseline surgical sub cutaneous and omental adipose tissue (to evaluate inflammation and fibrosis) as well as liver biopsy (to score non alcoholic hepatitis) will be analysed. 50 non obese patients will serve as controls. Adipose tissue stiffness measured with the device as well as fibrosis quantification on subcutaneous and omental adipose tissue will be assessed at baseline during programmed non inflammatory abdominal surgery Associations between all clinical and biological parameters will be assessed at the different point of the follow up.

More generally, this project might lead us to elucidate whether fibrosis in adipose tissue can predict surgery outcome in terms of weight loss and obesity related complications improvement. Also the investigators want to validate a new non invasive tool to measure adipose tissue fibrosis and check whether it can predict surgery outcomes.

Conditions

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Obesity Metabolic Diseases Fibrosis Body Weight

Keywords

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Obesity adipose tissue fibrosis Adipose tissue inflammation Low grade systemic inflammation non invasive device Bariatric surgery

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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biopsy

Obesity with BMI\> 40 kg/m² or obesity with BMI between \>35 kg/m² with comorbidities (OSA, type 2 diabetes, hypertension etc…)

Group Type EXPERIMENTAL

biopsy

Intervention Type PROCEDURE

adipose tissue biopsy (to evaluate inflammation and fibrosis)

healthy volunteers

biopsy during a surgery

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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biopsy

adipose tissue biopsy (to evaluate inflammation and fibrosis)

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

Obese population :

* Obesity with BMI\> 40 kg/m² or obesity with BMI \>35 kg/m² with comorbidities (OSA, type 2 diabetes, hypertension etc…)
* Age: 18-65
* weight stable for three months preceding surgery
* candidate to a sleeve or bypass or adjustable gastric banding

Controls:

* BMI\< 30 kg/m²
* Age: 18-65
* non inflammatory acute or chronic disease
* candidate to a programmed non inflammatory abdominal surgery

Exclusion Criteria

* Inflammatory disease
* Pregnancy
* cancer
* Drugs (AINS)
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Judith Aron-wisnewsky, MD

Role: PRINCIPAL_INVESTIGATOR

APHP

Karine Clement, MD, PhD

Role: STUDY_DIRECTOR

APHP

Locations

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Service de Chirurgie générale et digestive et d'oncologie du Pr Nordlinger -Ambroise Paré

Boulogne, , France

Site Status

Service de nutrition du Pr Basdevant -Pitié salpêtrière/ Institut Cardiometabolism and nutrition

Paris, , France

Site Status

Countries

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France

References

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Torres L, Camila Goncalves Miranda M, Dantas Martins V, Caixeta F, de Almeida Oliveira M, Martins Trindade L, Carvalho de Assis H, Nascimento V, Pinheiro Rosa N, Gomes E, Oliveira Almeida S, Marquet F, Genser L, Marcelin G, Clement K, Russo M, Maria Caetano Faria A, Uceli Maioli T. Obesity-induced hyperglycemia impairs oral tolerance induction and aggravates food allergy. Mucosal Immunol. 2023 Aug;16(4):513-526. doi: 10.1016/j.mucimm.2023.05.008. Epub 2023 Jun 10.

Reference Type DERIVED
PMID: 37302712 (View on PubMed)

Bel Lassen P, Nori N, Bedossa P, Genser L, Aron-Wisnewsky J, Poitou C, Surabattula R, Juul Nielsen M, Asser Karsdal M, Julie Leeming D, Schuppan D, Clement K. Fibrogenesis Marker PRO-C3 Is Higher in Advanced Liver Fibrosis and Improves in Patients Undergoing Bariatric Surgery. J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1356-e1366. doi: 10.1210/clinem/dgab897.

Reference Type DERIVED
PMID: 34905051 (View on PubMed)

Rouault C, Marcelin G, Adriouch S, Rose C, Genser L, Ambrosini M, Bichet JC, Zhang Y, Marquet F, Aron-Wisnewsky J, Poitou C, Andre S, Derumeaux G, Guerre-Millo M, Clement K. Senescence-associated beta-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity. Diabetologia. 2021 Jan;64(1):240-254. doi: 10.1007/s00125-020-05307-0. Epub 2020 Oct 30.

Reference Type DERIVED
PMID: 33125520 (View on PubMed)

Bel Lassen P, Charlotte F, Liu Y, Bedossa P, Le Naour G, Tordjman J, Poitou C, Bouillot JL, Genser L, Zucker JD, Sokolovska N, Aron-Wisnewsky J, Clement K. The FAT Score, a Fibrosis Score of Adipose Tissue: Predicting Weight-Loss Outcome After Gastric Bypass. J Clin Endocrinol Metab. 2017 Jul 1;102(7):2443-2453. doi: 10.1210/jc.2017-00138.

Reference Type DERIVED
PMID: 28419237 (View on PubMed)

Liu Y, Aron-Wisnewsky J, Marcelin G, Genser L, Le Naour G, Torcivia A, Bauvois B, Bouchet S, Pelloux V, Sasso M, Miette V, Tordjman J, Clement K. Accumulation and Changes in Composition of Collagens in Subcutaneous Adipose Tissue After Bariatric Surgery. J Clin Endocrinol Metab. 2016 Jan;101(1):293-304. doi: 10.1210/jc.2015-3348. Epub 2015 Nov 19.

Reference Type DERIVED
PMID: 26583585 (View on PubMed)

Verger EO, Aron-Wisnewsky J, Dao MC, Kayser BD, Oppert JM, Bouillot JL, Torcivia A, Clement K. Micronutrient and Protein Deficiencies After Gastric Bypass and Sleeve Gastrectomy: a 1-year Follow-up. Obes Surg. 2016 Apr;26(4):785-96. doi: 10.1007/s11695-015-1803-7.

Reference Type DERIVED
PMID: 26205215 (View on PubMed)

Other Identifiers

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P100503

Identifier Type: -

Identifier Source: org_study_id