Original InvestigationHypertension and Acid-Base/Electrolyte DisordersTolvaptan and Neurocognitive Function in Mild to Moderate Chronic Hyponatremia: A Randomized Trial (INSIGHT)
Section snippets
Study Design
The Investigation of the Neurocognitive Impact of Sodium Improvement in Geriatric Hyponatremia: Efficacy and Safety of Tolvaptan (INSIGHT) was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, titration-to-effect trial (Table S1, available as online supplementary material). The trial consisted of a 30-day screening period, 21-day treatment period, and 7-day posttreatment period (Fig 1A). During the screening period, attempts were made to identify and eliminate the
Patients
In all, 57 men and women were enrolled at 16 US sites in September 2007 to March 2009; a total of 53 patients were analyzed for efficacy (26 tolvaptan and 27 placebo), and 57, for safety (29 tolvaptan and 28 placebo; Fig 2). The 2 patient groups were relatively well matched for relevant baseline characteristics (Table 1). Compared with normative values from age-matched individuals, patients in this trial at baseline had significantly impaired cognitive performance on measures of correct choice
Discussion
This trial demonstrated the effects of oral tolvaptan on correction of serum sodium concentrations to the normal range in adult patients with mild hyponatremia and the effects of this correction on measures of cognition, gait, and bone metabolism. Compared with normative values from age-matched individuals, study participants had impaired cognitive performance at baseline on measures of correct choice and speed of choice, impaired postural and gait stability, and reduced SF-12 physical
Acknowledgements
The INSIGHT Investigators are Otis Barnum, Natchitoches Hospital; Karthikeya Devireddy, KD Medical Group Inc; Howard Ellison, Rockdale Medical Research Associates; Miguel Franco, Memorial Clinical Associates; Francis Goldstein, Carolina Research Associates; Terrence C. Hack, Primary Care Cardiology Research Inc; Kianoosh Kaveh, Coastal Nephrology Associates Research Center; Ali Khojasteh, Columbia Comprehensive Care Clinic; John LaFata, Progressive Clinical Research; Michael J. Lillestol,
References (32)
- et al.
Epidemiology of hyponatremia
Semin Nephrol
(2009) Age and gender as risk factors for hyponatremia and hypernatremia
Clin Chim Acta
(2003)- et al.
Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits
Am J Med
(2006) - et al.
Current treatment practice and outcomes. Report of the hyponatremia registry
Kidney Int
(2015) - et al.
Practice effects on cognitive tasks: a major problem?
Lancet Neurol
(2002) Brain volume regulation in response to changes in osmolality
Neuroscience
(2010)- et al.
Hyponatremia causes large sustained reductions in brain content of multiple organic osmolytes in rats
Brain Res
(1991) - et al.
Hyponatremia independent of osteoporosis is associated with fracture occurrence
Clin J Am Soc Nephrol
(2010) - et al.
Mild hyponatremia as a risk factor for fractures: the Rotterdam Study
J Bone Miner Res
(2011) - et al.
Hyponatremia-induced osteoporosis
J Bone Miner Res
(2010)
Hyponatremia and fractures: findings from the Osteoporotic Fractures in Men Study
J Bone Miner Res
Hyponatremia and osteoporosis: insights from the Danish National Patient Registry
Osteoporos Int
Hyponatremia is associated with increased osteoporosis and bone fractures in a large US health system population
J Clin Endocrinol Metab
Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia
N Engl J Med
Oral tolvaptan is safe and effective in chronic hyponatremia
J Am Soc Nephrol
The Cognitive Drug Research computerised assessment system for demented patients: a validation study
Int J Geriatr Psychiatry
Cited by (46)
Hyponatremia Demystified: Integrating Physiology to Shape Clinical Practice
2023, Advances in Kidney Disease and HealthHyponatremia in the emergency department
2022, American Journal of Emergency MedicineCitation Excerpt :Moreover, hyponatremia was associated with worse results for neurocognitive function and motor performance tests such as the Mini-Mental-State, DemTect or TrailMaking test [66]. Interestingly, neurocognitive function deficits were reversible after correction of hyponatremia implying causality rather than a pure association [67]. For the emergency physician, it is essential to be wary of potential hyponatremia when dealing with elderly patients presenting to the ED with unspecific complaints or falls.
Hyponatremia as a risk factor for microvascular spasm following subarachnoid hemorrhage
2022, Experimental NeurologyThink FIRST to treat Dilutional Hyponatremia in Patients With Heart Failure
2020, Journal for Nurse PractitionersCitation Excerpt :Tolvaptan, a vasopressin receptor antagonist, decreases the osmolality of urine and indirectly causes aquaresis. This allows the medication to alleviate congestive symptoms without the loss of serum sodium.28,29 Original studies using vasopressin receptor antagonists for hyponatremia used conivaptan and showed that this drug was effective at correcting serum sodium levels.30-32
Allostasis and the Clinical Manifestations of Mild to Moderate Chronic Hyponatremia: No Good Adaptation Goes Unpunished
2019, American Journal of Kidney Diseases
Trial registration: www.ClinicalTrials.gov; study number: NCT00550459.
- ∗
A list of the INSIGHT Investigators appears in the Acknowledgements.