Acute Kidney InjuryPhase 4LSCAKINCT03056248
Lithium in Acute Kidney Injury
A Phase 4 study testing Lithium Carbonate in people with Acute Kidney Injury, run by Lifespan.
Trial summary
A growing body of pre-clinical evidence suggests that glycogen synthase kinase 3β (GSKβ) is implicated in the development and progression of acute kidney injury (AKI). Lithium is a naturally occurring standard inhibitor of GSKβ. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Injury
- What is being tested?
- Lithium Carbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2017to 1 Jan 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A male or female greater than 18 years
- Stable renal function with creatinine change <0.3mg/dl in the preceding 1 month prior to scheduled surgery
- Procedure such as aortic valve surgery, mitral valve surgery, coronary artery bypass grafting, or combination of the above mentioned procedures
- Have estimated glomerular filtration rate greater than or equal to 15ml/min/ 1.73m2 as calculated by chronic kidney disease Epidemiology Collaboration (CKD-EPI) formula
Who cannot join
- Subjects who:
- Are taking lithium prior to surgery for any reason
- Have ejection fraction of <30% prior to surgery
- Have estimated glomerular filtration rate <15ml/min/ 1.73m2 as calculated by chronic kidney disease Epidemiology Collaboration (CKD-EPI) formula
- Having cardiac surgery to be performed without using cardiopulmonary bypass
- Has ongoing sepsis or history of sepsis in the last 2 weeks, defined as having 2 of the following criteria T >38C or <36C, pulse rate >90/min, RR >20/min, WBC >12 or >10% polymorphonuclear cells plus a documented source
- Has documented rise in creatinine ≥ 0.3mg/dl in the preceding one month prior to surgery
Trial locations and contacts
No sites are listed yet.
sairah sharif contact
About this study
Official title: Lithium in Cardiac Surgery Related Acute Kidney Injury: A Pilot Study
A growing body of pre-clinical evidence suggests that glycogen synthase kinase 3β (GSKβ) is implicated in the development and progression of acute kidney injury (AKI). Lithium is a naturally occurring standard inhibitor of GSKβ. The purpose of this study is to examined if low dose lithium carbonate is able to reduce the incidence of AKI in patients undergoing cardiac surgery who are placed on cardiopulmonary bypass during surgery. We hypothesize that low dose lithium might reduce the incidence and duration of AKI in patients undergoing cardiac surgery who are on cardiopulmonary bypass.
Read the detailed description
Cardiac surgery associated acute kidney injury (CSA-AKI) is a significant problem. The prevalence varies from 0.3% to 22.9% depending on the definition of AKI. The pathogenesis of AKI in this population is multifactorial. Factors associated with AKI in such patients include increased age, preoperative elevated creatinine, presence of diabetes, reduced ejection fraction, increased body weight, and presence of carotid artery bruit, duration of cardiopulmonary bypass, aortic cross clamp time, and duration of surgery. CSA-AKI is an independent predictor of mortality, morbidity, increased length of stay and hospitalization costs. Moreover these patients are also at increased risk of chronic kidney disease and end stage renal failure in the future.
Various pharmacologic approaches that have been tried to prevent early CSA-AKI such as diuretics, vasodilators, and anti-inflammatory drugs. Fenoldopam, atrial natriuretic peptide, and brain natriuretic peptide have shown little renoprotection. However these strategies lack high quality evidence to support their use and are not standard of care. There is no strong evidence to suggest any single or multiple pharmacotherapy that significantly impacts in reducing CAS-AKI. Thus the current best therapy for CSA-AKI is prevention, supportive care, hemodynamic optimization and renal replacement therapy.
AKI is an extremely complex process involving multiple pathophysiologic pathways. Glycogen synthase kinase 3β (GSK3β) is implicated in many pathways beyond glycogen metabolism and has been shown to be an important player in the development of AKI . Lithium is a US Food and Drug Administration (FDA)-approved drug which has been used for over 50 years as first line agent to treat mood disorders. It is a standard inhibitor for GSK3β. Latest evidence in murine models of cisplatin-induced AKI and ischemia/reperfusion-induced AKI suggests that lithium treatment may attenuated kidney dysfunction and kidney histologic injury following AKI. Lithium was able to promote kidney tubular cell repair hence improvement of AKI in murine models. In addition, lithium has also been found to exert an anti-proteinuric and renal reparative effect. On this background we want to explore the potential preventive and therapeutic role of lithium carbonate in CSA- AKI.
- Conditions
- Acute Kidney Injury
- Being tested
- Placebo oral capsule, Lithium Carbonate
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo oral capsuleDrug
Also called Placebo
On day 0, the day of the cardiac surgery placebo will be given once On day 1, one day after cardiac surgery placebo will be given once On day 2, two days after cardiac surgery placebo will be given once
Lithium CarbonateDrug
Also called Lithium
On day 0, the day of the cardiac surgery oral lithium will be given at dose 900mg once On day 1, one day after cardiac surgery oral lithium will be given at dose 900mg once On day 2, two days after cardiac surgery oral lithium will be given 900mg once
| Study group | Role | What they receive |
|---|---|---|
| Lithium | Active comparator | Patients will be identified by chart review and be explained the purpose of the study and informed consent taken Receives: Drug: Lithium Carbonate |
| Placebo | Placebo comparator | Patients will be identified by chart review and be explained the purpose of the study and informed consent taken Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in serum creatinine mg/dl
Renal function
Measured: 1 month
Secondary outcomes (3)
Peak creatinine mg/dl
Renal function
Measured: 1 month
Neutrophil gelatinase-associated lipocalcin (NGAL) ng/ml
Renal function
Measured: 3 days
Kidney injury molecule-1 (KIM1) ng/ml
Renal function
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2017
- Study start1 Apr 2017 (estimated)
- Primary completion30 Dec 2017 (estimated)
- Study completion1 Jan 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized to lithium versus placebo and rates of acute kidney injury will be measured
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lifespan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sairah Sharif, Lifespan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03056248
- Sponsor's protocol ID
- 02116
- Acronym
- LSCAKI
- Status last verified
- Feb 2017
- First submitted
- 13 Feb 2017
- Last updated
- 17 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Reddy DS, Reddy MS. Serum Lithium Levels: Ideal Time for Sample Collection! Are We Doing it Right? Indian J Psychol Med. 2014 Jul;36(3):346-7. doi: 10.4103/0253-7176.135399.
PubMed 25035570Vives M, Wijeysundera D, Marczin N, Monedero P, Rao V. Cardiac surgery-associated acute kidney injury. Interact Cardiovasc Thorac Surg. 2014 May;18(5):637-45. doi: 10.1093/icvts/ivu014. Epub 2014 Feb 16.
PubMed 24535092Gammelager H, Christiansen CF, Johansen MB, Tonnesen E, Jespersen B, Sorensen HT. Five-year risk of end-stage renal disease among intensive care patients surviving dialysis-requiring acute kidney injury: a nationwide cohort study. Crit Care. 2013 Jul 22;17(4):R145. doi: 10.1186/cc12824.
PubMed 23876346Coleman MD, Shaefi S, Sladen RN. Preventing acute kidney injury after cardiac surgery. Curr Opin Anaesthesiol. 2011 Feb;24(1):70-6. doi: 10.1097/ACO.0b013e3283422ebc.
PubMed 21157303Gong R, Wang P, Dworkin L. What we need to know about the effect of lithium on the kidney. Am J Physiol Renal Physiol. 2016 Dec 1;311(6):F1168-F1171. doi: 10.1152/ajprenal.00145.2016. Epub 2016 Apr 27.
PubMed 27122541Bao H, Ge Y, Wang Z, Zhuang S, Dworkin L, Peng A, Gong R. Delayed administration of a single dose of lithium promotes recovery from AKI. J Am Soc Nephrol. 2014 Mar;25(3):488-500. doi: 10.1681/ASN.2013040350. Epub 2014 Jan 9.
PubMed 24408869Sharif S, Chen B, Brewster P, Chen T, Dworkin L, Gong R. Rationale and Design of Assessing the Effectiveness of Short-Term Low-Dose Lithium Therapy in Averting Cardiac Surgery-Associated Acute Kidney Injury: A Randomized, Double Blinded, Placebo Controlled Pilot Trial. Front Med (Lausanne). 2021 Jun 14;8:639402. doi: 10.3389/fmed.2021.639402. eCollection 2021.
PubMed 34195206
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lithium in Cardiac Surgery Related Acute Kidney Injury: A Pilot Study
- ClinicalTrials.gov ID
- NCT03056248
- Acronym / sponsor ID
- LSCAKI / 02116
- Conditions
- Acute Kidney Injury
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- LifespanUniversity, hospital or other
- Study start
- 1 Apr 2017 (estimated)
- Primary completion
- 30 Dec 2017 (estimated)
- Study completion
- 1 Jan 2018 (estimated)
- First posted
- 17 Feb 2017 (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.
A growing body of pre-clinical evidence suggests that glycogen synthase kinase 3β (GSKβ) is implicated in the development and progression of acute kidney injury (AKI). Lithium is a naturally occurring standard inhibitor of GSKβ. The purpose of this study is to examined if low dose lithium carbonate is able to reduce the incidence of AKI in patients undergoing cardiac surgery who are placed on cardiopulmonary bypass during surgery. We hypothesize that low dose lithium might reduce the incidence and duration of AKI in patients undergoing cardiac surgery who are on cardiopulmonary bypass.
Detailed description
Cardiac surgery associated acute kidney injury (CSA-AKI) is a significant problem. The prevalence varies from 0.3% to 22.9% depending on the definition of AKI. The pathogenesis of AKI in this population is multifactorial. Factors associated with AKI in such patients include increased age, preoperative elevated creatinine, presence of diabetes, reduced ejection fraction, increased body weight, and presence of carotid artery bruit, duration of cardiopulmonary bypass, aortic cross clamp time, and duration of surgery. CSA-AKI is an independent predictor of mortality, morbidity, increased length of stay and hospitalization costs. Moreover these patients are also at increased risk of chronic kidney disease and end stage renal failure in the future.
Various pharmacologic approaches that have been tried to prevent early CSA-AKI such as diuretics, vasodilators, and anti-inflammatory drugs. Fenoldopam, atrial natriuretic peptide, and brain natriuretic peptide have shown little renoprotection. However these strategies lack high quality evidence to support their use and are not standard of care. There is no strong evidence to suggest any single or multiple pharmacotherapy that significantly impacts in reducing CAS-AKI. Thus the current best therapy for CSA-AKI is prevention, supportive care, hemodynamic optimization and renal replacement therapy.
AKI is an extremely complex process involving multiple pathophysiologic pathways. Glycogen synthase kinase 3β (GSK3β) is implicated in many pathways beyond glycogen metabolism and has been shown to be an important player in the development of AKI . Lithium is a US Food and Drug Administration (FDA)-approved drug which has been used for over 50 years as first line agent to treat mood disorders. It is a standard inhibitor for GSK3β. Latest evidence in murine models of cisplatin-induced AKI and ischemia/reperfusion-induced AKI suggests that lithium treatment may attenuated kidney dysfunction and kidney histologic injury following AKI. Lithium was able to promote kidney tubular cell repair hence improvement of AKI in murine models. In addition, lithium has also been found to exert an anti-proteinuric and renal reparative effect. On this background we want to explore the potential preventive and therapeutic role of lithium carbonate in CSA- AKI.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Patients will be randomized to lithium versus placebo and rates of acute kidney injury will be measured
| Arm | Type | Receives |
|---|---|---|
| Lithium | Active comparator | Drug: Lithium CarbonatePatients will be identified by chart review and be explained the purpose of the study and informed consent taken |
| Placebo | Placebo comparator | Drug: Placebo oral capsulePatients will be identified by chart review and be explained the purpose of the study and informed consent taken |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- A male or female greater than 18 years
- Stable renal function with creatinine change <0.3mg/dl in the preceding 1 month prior to scheduled surgery
- Procedure such as aortic valve surgery, mitral valve surgery, coronary artery bypass grafting, or combination of the above mentioned procedures
- Have estimated glomerular filtration rate greater than or equal to 15ml/min/ 1.73m2 as calculated by chronic kidney disease Epidemiology Collaboration (CKD-EPI) formula
Key exclusion criteria (7 listed)
- Are taking lithium prior to surgery for any reason
- Have ejection fraction of <30% prior to surgery
- Have estimated glomerular filtration rate <15ml/min/ 1.73m2 as calculated by chronic kidney disease Epidemiology Collaboration (CKD-EPI) formula
- Having cardiac surgery to be performed without using cardiopulmonary bypass
- Has ongoing sepsis or history of sepsis in the last 2 weeks, defined as having 2 of the following criteria T >38C or <36C, pulse rate >90/min, RR >20/min, WBC >12 or >10% polymorphonuclear cells plus a documented source
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 |
|---|---|---|
| Placebo oral capsuleAlso: PlaceboOn day 0, the day of the cardiac surgery placebo will be given once On day 1, one day after cardiac surgery placebo will be given once On day 2, two days after cardiac surgery placebo will be given once | Drug | Placebo |
| Lithium CarbonateAlso: LithiumOn day 0, the day of the cardiac surgery oral lithium will be given at dose 900mg once On day 1, one day after cardiac surgery oral lithium will be given at dose 900mg once On day 2, two days after cardiac surgery oral lithium will be given 900mg once | Drug | Lithium |
Primary outcome
Change in serum creatinine mg/dl
Time frame: 1 month
Renal function
3 secondary outcomes
Peak creatinine mg/dl
Time frame: 1 month
Neutrophil gelatinase-associated lipocalcin (NGAL) ng/ml
Time frame: 3 days
Kidney injury molecule-1 (KIM1) ng/ml
Time frame: 3 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2017.
- Results publication: PubMed 25035570Reddy DS, Reddy MS. Serum Lithium Levels: Ideal Time for Sample Collection! Are We Doing it Right? Indian J Psychol Med. 2014 Jul;36(3):346-7. doi: 10.4103/0253-7176.135399.
- Results publication: PubMed 24535092Vives M, Wijeysundera D, Marczin N, Monedero P, Rao V. Cardiac surgery-associated acute kidney injury. Interact Cardiovasc Thorac Surg. 2014 May;18(5):637-45. doi: 10.1093/icvts/ivu014. Epub 2014 Feb 16.
- Results publication: PubMed 23876346Gammelager H, Christiansen CF, Johansen MB, Tonnesen E, Jespersen B, Sorensen HT. Five-year risk of end-stage renal disease among intensive care patients surviving dialysis-requiring acute kidney injury: a nationwide cohort study. Crit Care. 2013 Jul 22;17(4):R145. doi: 10.1186/cc12824.
- Results publication: PubMed 21157303Coleman MD, Shaefi S, Sladen RN. Preventing acute kidney injury after cardiac surgery. Curr Opin Anaesthesiol. 2011 Feb;24(1):70-6. doi: 10.1097/ACO.0b013e3283422ebc.
- Results publication: PubMed 27122541Gong R, Wang P, Dworkin L. What we need to know about the effect of lithium on the kidney. Am J Physiol Renal Physiol. 2016 Dec 1;311(6):F1168-F1171. doi: 10.1152/ajprenal.00145.2016. Epub 2016 Apr 27.
- Results publication: PubMed 24408869Bao H, Ge Y, Wang Z, Zhuang S, Dworkin L, Peng A, Gong R. Delayed administration of a single dose of lithium promotes recovery from AKI. J Am Soc Nephrol. 2014 Mar;25(3):488-500. doi: 10.1681/ASN.2013040350. Epub 2014 Jan 9.
- Derived from this study: PubMed 34195206Sharif S, Chen B, Brewster P, Chen T, Dworkin L, Gong R. Rationale and Design of Assessing the Effectiveness of Short-Term Low-Dose Lithium Therapy in Averting Cardiac Surgery-Associated Acute Kidney Injury: A Randomized, Double Blinded, Placebo Controlled Pilot Trial. Front Med (Lausanne). 2021 Jun 14;8:639402. doi: 10.3389/fmed.2021.639402. eCollection 2021.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
sairah sharif contact
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lithium Carbonate in people with Acute Kidney Injury, run by Lifespan.
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 7 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: status not confirmed, as of the sponsor's last update on 17 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact sairah sharif (sairah.sharif1@gmail.com; sairah.sharif@lifespan.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in serum creatinine mg/dl (time frame: 1 month). 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 NCT03056248, which also lists 7 linked publications.
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 17 Feb 2017; AzTrials last refreshed its copy on 1 Nov 2026.