ESRDPhase 2INSPIREDNCT02278562

Nutrition, Inflammation and Insulin Resistance in End Stage Renal Disease-Aim 2

A Phase 2 study testing anakinra and actos in people with ESRD, run by VA Office of Research and Development at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

By 2030 an estimated 2 million people in the US will need dialysis or transplantation for advanced kidney failure. An even more disturbing statistic is that mortality in End Stage Renal Disease (ESRD) is six times higher than in the general Medicare population with adjustment for age, gender and ethnicity. Read more about this study

Who is it for?: Ages 21 years and older
Conditions the study is for: ESRD
What is being tested?: anakinra and actos
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 33 participants
Where: 1 siteUnited States
Study dates: 22 Oct 2014to 1 Mar 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 21 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients on CHD undergoing three time a week therapy for more than 6 months;
Age 21 years old;
Acceptable dialysis adequacy (spKt/V > 1.2);
A patent, well-functioning, arterio-venous dialysis access;
Ability to give informed consent;
Life expectancy greater than 6 months;
BMI >=20 and <=45.

Who cannot join

Pregnancy;
Intolerance or allergy to the study medication (including the metabolic clamp studies);
Severe, unstable, active inflammatory disease (active infection, active connective tissue disorder), active cancer or cancer history in the prior 5 years except skin cancer, AIDS-HIV, active or history of liver disease (including hepatitis B virus and hepatitis C virus);
Hospitalization or infection within 1 month prior to the study;
Patients receiving steroids and/or other immunosuppressive agents (Prednisone > 5 mg/day; excluding inhaled and topical steroids);
Diabetes Mellitus on insulin therapy;

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Previous history of tuberculosis (TB) with or without documented adequate therapy;
Patients with recent close exposure to an individual with active TB;
Females using oral contraceptives;
Patients with New York Heart Association (NYHA) Class III or IV heart failure;
Patients with a history of angina, myocardial infarction, transient ischemic attacks, or strokes within the last 6 months.

Trial locations and contacts

1 site in 1 country.

United States1 site

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN
Nashville, Tennessee, 37212-2637

Other trials in United States

About this study

Official title: Nutrition, Inflammation and Insulin Resistance in End-Stage Renal Disease

Despite its well-recognized occurrence, the etiology and the mechanisms leading to protein energy wasting observed in chronic hemodialysis patients cannot be attributed to any single factor. However, irrespective of the specific etiologic mechanisms, it appears that the common pathway for all the metabolic derangements is related to exaggerated protein degradation relative to protein synthesis (47).

Two well-recognized and presumably interrelated metabolic abnormalities, insulin resistance and chronic inflammation, may be the major determinants of protein catabolism in coronary heart disease (CHD) patients. There are no studies examining the effects of anti-inflammatory interventions and/or insulin sensitizers on protein homeostasis in CHD. Due to their established anti-inflammatory and other pleiotropic effects, Interleukin-1 receptor antagonist Anakinra and insulin sensitizer peroxisome proliferator-activated receptors (PPAR) agonist Actos represent two such promising interventions. By modulating inflammatory response and insulin signaling through two pharmacological interventions, the investigators will have the unique opportunity to clarify mechanisms contributing of these two particular metabolic derangements in the development of protein energy wasting observed in chronic hemodialysis patients.

The overall goal is to elucidate the mechanisms by which chronic inflammation and insulin resistance influence the development of protein energy wasting in hemodialysis patients.

Specific Aim: To test the hypothesis that inhibiting inflammatory response by administration of an Interleukin1receptor antagonist (Anakinra) or increasing insulin sensitivity by administration of a PPAR agonist (Actos) will improve net protein metabolism.

Hypothesis: The chronic inflammatory component of protein energy wasting (PEW) observed in hemodialysis patients is, at least in part, mediated by insulin resistance.

Interim analysis may be performed (no specific plan at this time).

Conditions: ESRD
Being tested: anakinra, actos, placebo
Medical subject headings: Kidney Failure, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

anakinraDrug
100 mg in syringes; administered subcutaneously 3 times a week for 12 weeks (3 months)
actosDrug
30 mg capsules; administered orally 1 capsule per day for 12 weeks (3 months)
placeboOther
placebo capsules and injection

Study groups in NCT02278562
Study group	Role	What they receive
anakinra	Active comparator	100 mg of Anakinra in syringes administered subcutaneously 3 times a week for 3 months and lactose (placebo) in capsules administered orally 1 capsule per day for 3 months Receives: Drug: anakinra
actos	Active comparator	Normal saline (placebo) in syringes administered subcutaneously 3 times a week for 3 months and 30 mg of Actos in capsules administered orally 1 capsule per day for 3 months Receives: Drug: actos
placebo 1 and 2	Placebo comparator	Normal saline (placebo) in syringes administered subcutaneously 3 times a week for 3 months and lactose (placebo) in capsules administered orally 1 capsule per day for 3 months Receives: Other: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Leucine Disposal Rate (LDR)
LDR is a sensitive laboratory assessment of amino acid metabolism
Measured: baseline and 3 months

Secondary outcomes (2)

Change in Whole-body Net Protein Balance
Whole-body net protein balance is the difference between protein synthesis (anabolism) and protein breakdown (catabolism) in the whole body
Measured: baseline and 3 months
Change in Skeletal Muscle Net Protein Balance
Skeletal muscle net protein balance is the difference between protein synthesis (anabolism) and protein breakdown (catabolism) in the skeletal muscles.
Measured: baseline and 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Oct 20141 Mar 2017

First posted30 Oct 2014 (estimated)
Study start22 Oct 2014
Primary completion1 Mar 2017
Study completion1 Mar 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for ESRDStudies of the same condition, open and under way.
More trials run by VA Office of Research and DevelopmentThe 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 33 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02278562
Sponsor's protocol ID: NEPH-011-11S
Acronym: INSPIRED
Status last verified: Jan 2025
First submitted: 28 Oct 2014
Last updated: 6 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Ertuglu LA, Deger SM, Alsouqi A, Hung A, Gamboa J, Mambungu C, Sha F, Siew E, Abumrad NN, Ikizler TA. A randomized controlled pilot trial of anakinra and pioglitazone for protein metabolism in patients on maintenance haemodialysis. J Cachexia Sarcopenia Muscle. 2024 Feb;15(1):401-411. doi: 10.1002/jcsm.13395. Epub 2024 Jan 4.
PubMed 38178557

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
RecruitingPhase 1
Serial Amnioinfusions as Regenerative Therapy for Pulmonary Hypoplasia
Renal Failure Congenital, Congenital Renal Anomaly Nos
Recruiting
NightWare and Cardiovascular Health in Women With PTSD
Post Traumatic Stress Disorder, Cardiovascular Diseases
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)

All ESRD trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Nutrition, Inflammation and Insulin Resistance in End-Stage Renal Disease
ClinicalTrials.gov ID: NCT02278562
Acronym / sponsor ID: INSPIRED / NEPH-011-11S
Conditions: ESRD
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 33 participants (actual)
Lead sponsor: VA Office of Research and DevelopmentUS federal agency
Study start: 22 Oct 2014 (actual)
Primary completion: 1 Mar 2017 (actual)
Study completion: 1 Mar 2017 (actual)
First posted: 30 Oct 2014 (estimated)
Results: Posted 2 Apr 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The overall goal is to elucidate the mechanisms by which chronic inflammation and insulin resistance influence the development of protein energy wasting in hemodialysis patients.

Hypothesis: The chronic inflammatory component of protein energy wasting (PEW) observed in hemodialysis patients is, at least in part, mediated by insulin resistance.

Interim analysis may be performed (no specific plan at this time).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
anakinra	Active comparator	Drug: anakinra100 mg of Anakinra in syringes administered subcutaneously 3 times a week for 3 months and lactose (placebo) in capsules administered orally 1 capsule per day for 3 months
actos	Active comparator	Drug: actosNormal saline (placebo) in syringes administered subcutaneously 3 times a week for 3 months and 30 mg of Actos in capsules administered orally 1 capsule per day for 3 months
placebo 1 and 2	Placebo comparator	Other: placeboNormal saline (placebo) in syringes administered subcutaneously 3 times a week for 3 months and lactose (placebo) in capsules administered orally 1 capsule per day for 3 months

Who may qualify

Ages: 21 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Patients on CHD undergoing three time a week therapy for more than 6 months;
Age 21 years old;
Acceptable dialysis adequacy (spKt/V > 1.2);
A patent, well-functioning, arterio-venous dialysis access;
Ability to give informed consent;

Key exclusion criteria (11 listed)

Pregnancy;
Intolerance or allergy to the study medication (including the metabolic clamp studies);
Severe, unstable, active inflammatory disease (active infection, active connective tissue disorder), active cancer or cancer history in the prior 5 years except skin cancer, AIDS-HIV, active or history of liver disease (including hepatitis B virus and hepatitis C virus);
Hospitalization or infection within 1 month prior to the study;
Patients receiving steroids and/or other immunosuppressive agents (Prednisone > 5 mg/day; excluding inhaled and topical steroids);

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
anakinra100 mg in syringes; administered subcutaneously 3 times a week for 12 weeks (3 months)	Drug	anakinra
actos30 mg capsules; administered orally 1 capsule per day for 12 weeks (3 months)	Drug	actos
placeboplacebo capsules and injection	Other	placebo 1 and 2

Primary outcome

Change in Leucine Disposal Rate (LDR)
Time frame: baseline and 3 months
LDR is a sensitive laboratory assessment of amino acid metabolism

2 secondary outcomes

Change in Whole-body Net Protein Balance
Time frame: baseline and 3 months
Change in Skeletal Muscle Net Protein Balance
Time frame: baseline and 3 months

Results and safety

Results posted to the registry on 2 Apr 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Anakinra	9	9
Actos	7	7
Placebo 1 and 2	8	8

Primary outcome: Change in Leucine Disposal Rate (LDR)

Time frame: baseline and 3 months. Median (Inter-Quartile Range). Unit: mg/kg/min

Measure	Anakinra n = 9	Actos n = 7	Placebo 1 and 2 n = 8
Value	-0.011 (-0.014 to -0.001)	0.005 (-0.026 to 0.015)	0.001 (-0.008 to 0.008)

Anakinra vs Placebo 1 and 2: p = 0.37, Wilcoxon Rank-Sum
Actos vs Placebo 1 and 2: p = 0.955, Wilcoxon Rank-Sum

Population analysed: The number of participants for analysis was based on those subjects who completed the 3-month study. The analysis was per protocol.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 3 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Anakinra	0 of 9 (0%)	5 of 9 (55.6%)	0 of 9
Actos	0 of 7 (0%)	1 of 7 (14.3%)	0 of 7
Placebo 1 and 2	0 of 8 (0%)	2 of 8 (25%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 38178557Ertuglu LA, Deger SM, Alsouqi A, Hung A, Gamboa J, Mambungu C, Sha F, Siew E, Abumrad NN, Ikizler TA. A randomized controlled pilot trial of anakinra and pioglitazone for protein metabolism in patients on maintenance haemodialysis. J Cachexia Sarcopenia Muscle. 2024 Feb;15(1):401-411. doi: 10.1002/jcsm.13395. Epub 2024 Jan 4.
Individual participant dataSharing planned: No

Related trials for ESRD

Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
RecruitingPhase 1
Serial Amnioinfusions as Regenerative Therapy for Pulmonary Hypoplasia
Renal Failure Congenital, Congenital Renal Anomaly Nos
Recruiting
NightWare and Cardiovascular Health in Women With PTSD
Post Traumatic Stress Disorder, Cardiovascular Diseases
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)

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. This study is not recruiting at the moment.

Talat A Ikizler, MD principal investigator

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing anakinra and actos in people with ESRD, run by VA Office of Research and Development at 1 site in United States.

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 7 inclusion and 11 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: finished, as of the sponsor's last update on 6 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Leucine Disposal Rate (LDR) (time frame: baseline and 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02278562, which also lists 1 linked publication.

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 6 Feb 2025.