Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial.
BACKGROUND
Lithium is the gold-standard treatment for bipolar disorder, is highly effective in treating major depressive disorder, and has anti-suicidal properties. However, clinicians are increasingly avoiding lithium largely due to fears of renal toxicity. Nephrogenic Diabetes Insipidus (NDI) occurs in 15-20% of lithium users and predicts a 2-3 times increased risk of chronic kidney disease (CKD). We recently found that use of statins is associated with lower NDI risk in a cross-sectional study. In this current paper, we describe the methodology of a randomized controlled trial (RCT) to treat lithium-induced NDI using atorvastatin.


METHODS
We will conduct a 12-week, double-blind placebo-controlled RCT of atorvastatin for lithium-induced NDI at McGill University, Montreal, Canada. We will recruit 60 current lithium users, aged 18-85, who have indicators of NDI, which we defined as urine osmolality (UOsm) < 600 mOsm/kg after 10-h fluid restriction. We will randomize patients to atorvastatin (20 mg/day) or placebo for 12 weeks. We will examine whether this improves measures of NDI: UOsm and aquaporin (AQP2) excretion at 12-week follow-up, adjusted for baseline.


RESULTS
Not applicable.


CONCLUSION
The aim of this clinical trial is to provide preliminary data about the efficacy of atorvastatin in treating NDI. If successful, lithium could theoretically be used more safely in patients with a reduced subsequent risk of CKD, hypernatremia, and acute kidney injury (AKI). If future definitive trials confirm this, this could potentially allow more patients to benefit from lithium, while minimizing renal risk.


TRIAL REGISTRATION
ClinicalTrials.gov NCT02967653 . Registered in February 2017.
['Fotso Soh|Jocelyn|J|0000-0001-9706-995X', 'Torres-Platas|Susana G|SG|', 'Beaulieu|Serge|S|', 'Mantere|Outi|O|', 'Platt|Robert|R|', 'Mucsi|Istvan|I|', 'Saury|Sybille|S|', 'Renaud|Suzane|S|', 'Levinson|Andrea|A|', 'Andreazza|Ana C|AC|', 'Mulsant|Benoit H|BH|', 'Müller|Daniel|D|', 'Schaffer|Ayal|A|', 'Dols|Annemiek|A|', 'Cervantes|Pablo|P|', 'Low|Nancy Cp|NC|', 'Herrmann|Nathan|N|', 'Christensen|Birgitte M|BM|', 'Trepiccione|Francesco|F|', 'Rajji|Tarek|T|', 'Rej|Soham|S|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D000069059:Atorvastatin D001714:Bipolar Disorder D002170:Canada D003430:Cross-Sectional Studies D003865:Depressive Disorder, Major D018500:Diabetes Insipidus, Nephrogenic D004311:Double-Blind Method D005260:Female D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D007668:Kidney D018020:Lithium Compounds D008297:Male D008875:Middle Aged D055815:Young Adult
Atorvastatin Nephrogenic diabetes insipidus Lithium Placebo Kidney function Randomized clinical trial Urinary osmolality