Chronic Kidney FailureINTRANCT06887075
Systemic Activation of Inflammasomes and Frailty in Older Candidates to Kidney Transplantation
A study testing Blood sample and Geriatric assessment standardized in people with Chronic Kidney Failure and Frailty, run by University Hospital, Bordeaux at 3 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Chronic Kidney Failure, Frailty, Aging
- What is being tested?
- Blood sample and Geriatric assessment standardized
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 3 sitesFrance
- Study dates
- 15 Apr 2025to 15 Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
- Free, informed and written consent signed by the participant and the investigator (at the latest, on the day of inclusion and before any examination required by the research).
- Person affiliated or beneficiary of a social security scheme
Who cannot join
- Inclusion in an industrial study refusing co-inclusion in our study
- Person under guardianship, assisted decision-making or under temporary guardianship
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France3 sites
CHU de Bordeaux - Hôpital Pellegrin -
Bordeaux, France, 33076
Lionel COUZI, MD, PhD, 0556796107 ext. +33, lionel.couzi@chubordeaux.fr
Lionel COUZI, MD; PhD
CHU de Bordeaux, Hôpital Xavier Arnozan- Gérontologie Clinique
Pessac, France, 33600
Florent GUERVILLE, MD, 05 57 65 65 13 ext. +33, florent.guerville@chubordeaux.fr
Florent GUERVILLE, MD
CHU de Toulouse - Hôpital Rangueil
Toulouse, France, 31059
Aliénor Galinier, MD, 0561323379 ext. +33, galinier.al@chutoulouse.fr
Aliénor Galinier, MD
About this study
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.
Read the detailed description
Kidney transplantation (KT) benefit-risk ratio assessment is a challenge in a growing population of older patients with end-stage kidney disease. Chronic low-grade inflammation is a hallmark of biological aging and is associated with age-related diseases and frailty. Frailty is conceptually defined as an agerelated reduction in physiological reserve increasing vulnerability to stressors. A pre-KT frailty phenotype is associated with post-KT complications, including re-hospitalizations, delayed graft function, delirium and 5-year mortality. Taking pre-KT inflammation into account (serum level of CRP, IL6, sTNFR1) improves prediction of mortality on KT waiting-list, independently of comorbidity.
Molecular and cellular pathways of this inflammation are poorly known, and may involve inflammasomes. Inflammasomes are intra-cellular protein complexes whose assembly, upon stress signals, triggers maturation and release of pro-inflammatory cytokines named interleukine (IL)-1 and IL-18. Inflammasomes are involved in locomotor, cognitive and immune aging in mice, and systemic expression of inflammasomes genes is associated with mortality in older humans. Data is lacking about systemic activation of inflammasomes in older patients with end-stage kidney disease. Our main objective is to assess if pre-KT systemic activation of inflammasomes is associated with frailty in older candidates to KT.
We will measure systemic activation of inflammasomes in peripheral blood of older candidates to KT using cytokine bead-based multiplex assay, Single Molecule Array, intra-cytoplasmic staining, flow cytometry and RT-qPCR in peripheral blood mononuclear cells. Frailty will be measured using validated standardized criteria. A frailty phenotype is defined by at least 3 of the following criteria:
weight loss, exhaustion, muscle weakness, low physical activity, low gait speed.
- Conditions
- Chronic Kidney Failure, Frailty, Aging, Inflammation
- Being tested
- Blood sample, Geriatric assessment standardized
- Keywords
- Older persons, End-stage kidney disease, Kidney transplantation, Immune aging, Chronic low-grade inflammation, Inflammasomes, Frailty
- Medical subject headings
- Kidney Failure, Chronic, Frailty, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sampleBiological
- 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
Geriatric assessment standardizedBehavioural
- 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)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Biological: Blood sample; Behavioral: Geriatric assessment standardized |
What is being measured
The primary outcome is the main question the study is designed to answer.
IL1
Single Molecule Array for IL1
Measured: at recruitment (up to 30 days)
IL18
LUMINEX for IL18 in patient's sera
Measured: 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
Measured: 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
Measured: at recruitment (up to 30 days)
Weight
Frailty phenotype : Weight loss (unintentional, >4,5 kg during past year)
Measured: 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)
Measured: at enrollment (Day 0), at recruitment (up to 30 days)
Gait
Frailty phenotype : 4-meters gait speed, with sex and height-specific cutoffs
Measured: 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
Measured: at enrollment (day 0), at recruitment (up to 30 days)
Secondary outcomes (16)
Comorbidity
Comorbidity : Cumulative Illness Rating Scale (CIRS-G score)
Measured: at recruitment (up to 30 days)
decline
Screening for intrinsic capacity decline : first step of ICOPE program, adapted to the study
Measured: at recruitment (up to 30 days)
Physical performance
Physical performance : Short Physical Performance Battery (SPPB) score. The SPPB (Short Physical Performance Battery) is the sum of scores on three criteria: the balance test, the walking speed test and the chair lift test. This test assesses an individual's physical performance.
The sum of the scores for all the tests gives an overall performance score. A score below 8 indicates a risk of sarcopenia (or age-related muscular dystrophy).
Measured: at recruitment (up to 30 days)
Cognitive functions
Cognitive functions : Score Montreal Cognitive Assessment (MoCA) score The Montreal Cognitive Assessement (MoCA) is the most sensitive rapid assessment test, providing the most comprehensive evaluation (attention, concentration, executive functions, memory, language, capacitive-vesuo-constructive, abstraction, calculation, orientation) cognitive functions. It is tending to replace the MMSE in clinical practice.
A score of 26 (25 if cultural level ≤3 = primary diploma = CEP) is considered abnormal.
Measured: at recruitment (up to 30 days)
Depression
Depression : Geriatric Depression Scale (GDS-15 score) 0 - 5 points: normal 5-10 points: mild to moderate depression 11-15 points: severe depression
Measured: at recruitment (up to 30 days)
Nutrition
Nutrition : Mini Nutritional Assessment (MNA score)
- 12-14 points: MNA score indicates normal nutritional status.
- 8-11 points: the MNA score indicates a risk of malnutrition.
- 0-7 points: MNA score indicates malnutrition.
Measured: at recruitment (up to 30 days)
Snellen test
Sensory functions : Snellen test for vision
Measured: at recruitment (up to 30 days)
ADL
Dependency in activities of daily living : Activities of Daily Living ADL The original ADL scale scores each of the 6 items in 0/1, with 1 corresponding to independence and 0 to dependence. The total score ranges from 0 to 6.
An overall score can be calculated, ranging from 0 (totally dependent) to 6 (best possible independence).
Measured: at recruitment (up to 30 days)
Immunophenotyping
Immunophenotyping of peripheral lymphocytes, with a focus on proportions of naïve / central memory / effector memory / TEMRA cells, and markers of activation and senescence
Measured: at recruitment (up to 30 days)
CRP
Serum inflammatory markers : CRP
Measured: at recruitment (up to 30 days)
IL-6
Serum inflammatory markers : IL-6
Measured: at recruitment (up to 30 days)
MCP-1
Serum inflammatory markers : MCP-1
Measured: at recruitment (up to 30 days)
TNF
Serum inflammatory markers : TNF
Measured: at recruitment (up to 30 days)
sTNFR1
Serum inflammatory markers : sTNFR1
Measured: at recruitment (up to 30 days)
HHIES questionnaire
Sensory functions : Hearing Handicap Inventory for the Elderly Screening (HHIES) questionnaire for hearing. The higher the score, the greater the likelihood of hearing loss
Measured: at recruitment (up to 30 days)
IADL
Dependency in activities of daily living : IADL scores
Measured: at recruitment (up to 30 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2025
- Study start15 Apr 2025 (estimated)
- Primary completion15 Feb 2027 (estimated)
- Study completion15 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney FailureStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Florent GUERVILLE, MD, Principal investigator, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06887075
- Sponsor's protocol ID
- CHUBX 2022/31
- Acronym
- INTRA
- Status last verified
- Jan 2025
- First submitted
- 22 Jan 2025
- Last updated
- 20 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systemic Activation of Inflammasomes and Frailty in Older Candidates to Kidney Transplantation
- ClinicalTrials.gov ID
- NCT06887075
- Acronym / sponsor ID
- INTRA / CHUBX 2022/31
- Conditions
- Chronic Kidney Failure, Frailty, Aging, Inflammation
- Keywords
- Older persons, End-stage kidney disease, Kidney transplantation, Immune aging, Chronic low-grade inflammation, Inflammasomes, Frailty
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 15 Apr 2025 (estimated)
- Primary completion
- 15 Feb 2027 (estimated)
- Study completion
- 15 Feb 2027 (estimated)
- First posted
- 20 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Kidney transplantation (KT) benefit-risk ratio assessment is a challenge in a growing population of older patients with end-stage kidney disease. Chronic low-grade inflammation is a hallmark of biological aging and is associated with age-related diseases and frailty. Frailty is conceptually defined as an agerelated reduction in physiological reserve increasing vulnerability to stressors. A pre-KT frailty phenotype is associated with post-KT complications, including re-hospitalizations, delayed graft function, delirium and 5-year mortality. Taking pre-KT inflammation into account (serum level of CRP, IL6, sTNFR1) improves prediction of mortality on KT waiting-list, independently of comorbidity.
Molecular and cellular pathways of this inflammation are poorly known, and may involve inflammasomes. Inflammasomes are intra-cellular protein complexes whose assembly, upon stress signals, triggers maturation and release of pro-inflammatory cytokines named interleukine (IL)-1 and IL-18. Inflammasomes are involved in locomotor, cognitive and immune aging in mice, and systemic expression of inflammasomes genes is associated with mortality in older humans. Data is lacking about systemic activation of inflammasomes in older patients with end-stage kidney disease. Our main objective is to assess if pre-KT systemic activation of inflammasomes is associated with frailty in older candidates to KT.
We will measure systemic activation of inflammasomes in peripheral blood of older candidates to KT using cytokine bead-based multiplex assay, Single Molecule Array, intra-cytoplasmic staining, flow cytometry and RT-qPCR in peripheral blood mononuclear cells. Frailty will be measured using validated standardized criteria. A frailty phenotype is defined by at least 3 of the following criteria:
weight loss, exhaustion, muscle weakness, low physical activity, low gait speed.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Frail Patients | Active comparator | Biological: Blood sample, Behavioral: Geriatric assessment standardizedFrailty 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 |
| non frail patients | Active comparator | Biological: Blood sample, Behavioral: Geriatric assessment standardizedPatients will be considered non-fragile if they present 0 to 2 criteria |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
Key exclusion criteria (2 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood sample* 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 | Biological | Frail Patients, non frail patients |
| Geriatric assessment standardized* 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) | Behavioural | Frail Patients, non frail patients |
Primary outcome
IL1
Time frame: at recruitment (up to 30 days)
Single Molecule Array for IL1
IL18
Time frame: at recruitment (up to 30 days)
LUMINEX for IL18 in patient's sera
inflammasomes genes
Time frame: at recruitment (up to 30 days)
RT-qPCR for inflammasomes genes (NLRP3, NLRC4, NLRC5, AIM2, ASC, casp1, IL1b, IL18) expression among peripheral blood mononuclear cells
inflammasome platform
Time frame: at recruitment (up to 30 days)
Assembly of the inflammasome platform will be measured in monocytes using intra-cellular staining of the ASC protein and flow cytometry
Weight
Time frame: at enrollment (Day 0), at recruitment (up to 30 days)
Frailty phenotype : Weight loss (unintentional, >4,5 kg during past year)
Activity
Time frame: at enrollment (Day 0), at recruitment (up to 30 days)
Frailty phenotype : Physical activity <383 kcal/week (men) or <270 kcal/week (women), measured using a standardized questionnaire (IPAQ)
Gait
Time frame: at enrollment (day 0), at recruitment (up to 30 days)
Frailty phenotype : 4-meters gait speed, with sex and height-specific cutoffs
Handgrip strength
Time frame: at enrollment (day 0), at recruitment (up to 30 days)
Frailty phenotype : Handgrip strength, measured using a dynamometer, with sex and BMI-specific cutoffs
16 secondary outcomes
Comorbidity
Time frame: at recruitment (up to 30 days)
decline
Time frame: at recruitment (up to 30 days)
Physical performance
Time frame: at recruitment (up to 30 days)
Cognitive functions
Time frame: at recruitment (up to 30 days)
Depression
Time frame: at recruitment (up to 30 days)
Nutrition
Time frame: at recruitment (up to 30 days)
Snellen test
Time frame: at recruitment (up to 30 days)
ADL
Time frame: at recruitment (up to 30 days)
Immunophenotyping
Time frame: at recruitment (up to 30 days)
CRP
Time frame: at recruitment (up to 30 days)
IL-6
Time frame: at recruitment (up to 30 days)
MCP-1
Time frame: at recruitment (up to 30 days)
TNF
Time frame: at recruitment (up to 30 days)
sTNFR1
Time frame: at recruitment (up to 30 days)
HHIES questionnaire
Time frame: at recruitment (up to 30 days)
IADL
Time frame: at recruitment (up to 30 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Florent GUERVILLE, MD principal investigator
University Hospital, Bordeaux
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sample and Geriatric assessment standardized in people with Chronic Kidney Failure and Frailty, run by University Hospital, Bordeaux at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Florent GUERVILLE, MD (05 57 65 65 53 ext. +33, florent.guerville@chu-bordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IL1 (time frame: at recruitment (up to 30 days)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2025.