Systemic Activation of Inflammasomes and Frailty in Older Candidates to Kidney Transplantation

NCT06887075 | Not Yet Recruiting DMC

• 1 other identifier: CHUBX 2022/31
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

Kidney transplantation (KT) benefit-risk ratio assessment is a challenge in a growing population of older patients with end-stage kidney disease. A pre-KT frailty phenotype has been found predictive of post-KT complications, but biological mechanisms of frailty are poorly known is these patients. Frailty is associated with chronic low-grade inflammation in the older general population, possibly through the inflammasome pathway. Our main objective is to assess if systemic activation of inflammasomes is associated with frailty in older candidates to KT.

Conditions

Chronic Kidney Failure; Frailty; Aging; Inflammation

Keywords

Older persons; End-stage kidney disease; Kidney transplantation; Immune aging; Chronic low-grade inflammation; Inflammasomes; Frailty

Outcome Measures

Primary Outcomes (8)

• IL1

  Single Molecule Array for IL1

  at recruitment (up to 30 days)

• IL18

  LUMINEX for IL18 in patient's sera

  at recruitment (up to 30 days)

• inflammasomes genes

  RT-qPCR for inflammasomes genes (NLRP3, NLRC4, NLRC5, AIM2, ASC, casp1, IL1b, IL18) expression among peripheral blood mononuclear cells

  at recruitment (up to 30 days)

• inflammasome platform

  Assembly of the inflammasome platform will be measured in monocytes using intra-cellular staining of the ASC protein and flow cytometry

  at recruitment (up to 30 days)

• Weight

  Frailty phenotype : Weight loss (unintentional, \>4,5 kg during past year)

  at enrollment (Day 0), at recruitment (up to 30 days)

• Activity

  Frailty phenotype : Physical activity \<383 kcal/week (men) or \<270 kcal/week (women), measured using a standardized questionnaire (IPAQ)

  at enrollment (Day 0), at recruitment (up to 30 days)

• Gait

  Frailty phenotype : 4-meters gait speed, with sex and height-specific cutoffs

  at enrollment (day 0), at recruitment (up to 30 days)

• Handgrip strength

  Frailty phenotype : Handgrip strength, measured using a dynamometer, with sex and BMI-specific cutoffs

  at enrollment (day 0), at recruitment (up to 30 days)

Secondary Outcomes (16)

• Comorbidity

  at recruitment (up to 30 days)

• decline

  at recruitment (up to 30 days)

• Physical performance

  at recruitment (up to 30 days)

• Cognitive functions

  at recruitment (up to 30 days)

• Depression

  at recruitment (up to 30 days)

Study Arms (2)

Frail Patients

ACTIVE COMPARATOR

Frailty will be measured clinically using reference criteria in the general population and validated in Kidney Transplantation (KT), i.e. predictive of post-KT complications: delayed recovery of graft function, graft function, early re-hospitalization, occurrence of post-operative confusion, mortality. Fragile patients present at least 3 out of 5 criteria

Biological: Blood sample; Behavioral: Geriatric assessment standardized

non frail patients

ACTIVE COMPARATOR

Patients will be considered non-fragile if they present 0 to 2 criteria

Biological: Blood sample; Behavioral: Geriatric assessment standardized

Interventions

Blood sample BIOLOGICAL

* Immunophenotyping of peripheral lymphocytes, with a focus on proportions of naïve / central memory / effector memory / TEMRA cells, and markers of activation and senescence * Serum inflammatory markers : CRP, IL-6, MCP-1, TNF, sTNFR1 * Single Molecule Array for IL1 and LUMINEX for IL18 in patient's sera * RT-qPCR for inflammasomes genes (NLRP3, NLRC4, NLRC5, AIM2, ASC, casp1, IL1b, IL18) expression among peripheral blood mononuclear cells * Assembly of the inflammasome platform will be measured in monocytes using intra-cellular staining of the ASC protein and flow cytometry

Frail Patients; non frail patients

Geriatric assessment standardized BEHAVIORAL

* Exhaustion (2 standardized questions) * Physical activity \<383 kcal/week (men) or \<270 kcal/week (women), measured using a standardized questionnaire (IPAQ) * 4-meters gait speed, with sex and height-specific cutoffs * Handgrip strength, measured using a dynamometer, with sex and BMI-sp Comorbidity (CIRS-G score ) * Screening for intrinsic capacity decline (first step of ICOPE program, adapted to the study, ) * Physical performance (SPPB score ) * Cognitive functions (MoCA score ), * Depression (GDS-15 score ), * Nutrition (MNA score ) * Sensory functions (Snellen test for vision, HHIES questionnaire for hearing) -- Dependency in activities of daily living (ADL and IADL scores)

Frail Patients; non frail patients

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age ≥ 70
• Patient candidate to kidney transplantation (during assessment for inscription on the waiting-list, or during waiting time after effective inscription), without absolute contraindication
• Person affiliated or beneficiary of a social security scheme

You may not qualify if:

• Person under guardianship, assisted decision-making or under temporary guardianship

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (3)

CHU de Bordeaux - Hôpital Pellegrin -

Bordeaux, France, 33076, France

Location

CHU de Bordeaux, Hôpital Xavier Arnozan- Gérontologie Clinique

Pessac, France, 33600, France

Location

CHU de Toulouse - Hôpital Rangueil

Toulouse, France, 31059, France

Location

MeSH Terms

Conditions

Kidney Failure, Chronic; Frailty; Inflammation

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Florent GUERVILLE, MD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Florent GUERVILLE, MD

CONTACT

05 57 65 65 53; florent.guerville@chu-bordeaux.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: March 20, 2025
• Study Start: April 15, 2025
• Primary Completion (Estimated): February 15, 2027
• Study Completion (Estimated): February 15, 2027
• Last Updated: March 20, 2025

Record last verified: 2025-01

Locations

FR (3)