Clinical trial NCT03371199: The Association Between Hyponatremia and Osteoporosis in Patients With Epilepsy.
Official title: The Effect of Normalization of Sodium on Bone Markers in Patients With Epilepsy. A Randomized Single-blinded Placebo-controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hyponatremia
Metabolic Bone Disease
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2017-12-13
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The study investigates the association between normalization of serum sodium levels and bone markers in patients with epilepsy and chronic hyponatremia.

The study is a randomized, single blinded, placebo controlled study where participants will be randomized to either treatment with salt tablets or placebo tablets through 4 months. At the beginning and end of the 4 months bone markers will be measured.

The investigators null-hypothesis is that there will be no difference in bone markers before or after the intervention.


Eligibility criteria: Inclusion Criteria:

* Epilepsy requiring treatment for at least 2 years
* Known hyponatremia (2 subsequent s-sodium values \< 136 mmol/l)
* Age 18-80 years
* Danish speaking
* Signed form of prior consent

Exclusion Criteria:

* Pregnancy and breastfeeding
* Known osteoporosis. DXA scan \< -2.5 T-score. Z-score is used for patients 50 years or younger.
* Undergoing treatment for osteoporosis
* Undergoing treatment with salt tablets
* Known SIADH
* Severe concomitant disease such as cancer or ischemic heart disease
* Alcohol, drug or substance abuse

Primary outcomes:
measure: CTX1 change
timeFrame: At baseline and after 4 months intervention
Secondary outcomes:
measure: P1NP change
timeFrame: At baseline and after 4 months intervention
measure: DXA scan change
timeFrame: At baseline and after 4 months intervention
measure: Cognitive function change
timeFrame: At baseline and after 4 months intervention
measure: Life quality change
timeFrame: At baseline and after 4 months intervention
measure: Change in daily pains
timeFrame: At baseline and after 4 months intervention
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Rigshospitalet Glostrup
Study officials:
affiliation: Senoir consultant
name: Noémi B Andersen, DMSc, MD
role: STUDY_CHAIR
References:
citation: Fedorenko M, Wagner ML, Wu BY. Survey of risk factors for osteoporosis and osteoprotective behaviors among patients with epilepsy. Epilepsy Behav. 2015 Apr;45:217-22. doi: 10.1016/j.yebeh.2015.01.021. Epub 2015 Mar 24.
citation: Maraka S, Kennel KA. Bisphosphonates for the prevention and treatment of osteoporosis. BMJ. 2015 Sep 2;351:h3783. doi: 10.1136/bmj.h3783.
citation: Darba J, Kaskens L, Perez-Alvarez N, Palacios S, Neyro JL, Rejas J. Disability-adjusted-life-years losses in postmenopausal women with osteoporosis: a burden of illness study. BMC Public Health. 2015 Apr 2;15:324. doi: 10.1186/s12889-015-1684-7.
citation: Wu FJ, Sheu SY, Lin HC. Osteoporosis is associated with antiepileptic drugs: a population-based study. Epileptic Disord. 2014 Sep;16(3):333-42. doi: 10.1684/epd.2014.0673.
citation: Asconape JJ. Some common issues in the use of antiepileptic drugs. Semin Neurol. 2002 Mar;22(1):27-39. doi: 10.1055/s-2002-33046.
citation: Vasikaran S, Eastell R, Bruyere O, Foldes AJ, Garnero P, Griesmacher A, McClung M, Morris HA, Silverman S, Trenti T, Wahl DA, Cooper C, Kanis JA; IOF-IFCC Bone Marker Standards Working Group. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. 2011 Feb;22(2):391-420. doi: 10.1007/s00198-010-1501-1. Epub 2010 Dec 24.
citation: Sejling AS, Thorsteinsson AL, Pedersen-Bjergaard U, Eiken P. Recovery from SIADH-associated osteoporosis: a case report. J Clin Endocrinol Metab. 2014 Oct;99(10):3527-30. doi: 10.1210/jc.2014-1572. Epub 2014 Jun 27.
citation: Sejling AS, Pedersen-Bjergaard U, Eiken P. Syndrome of inappropriate ADH secretion and severe osteoporosis. J Clin Endocrinol Metab. 2012 Dec;97(12):4306-10. doi: 10.1210/jc.2012-2031. Epub 2012 Oct 17.
citation: Verbalis JG, Barsony J, Sugimura Y, Tian Y, Adams DJ, Carter EA, Resnick HE. Hyponatremia-induced osteoporosis. J Bone Miner Res. 2010 Mar;25(3):554-63. doi: 10.1359/jbmr.090827.
citation: Barsony J, Sugimura Y, Verbalis JG. Osteoclast response to low extracellular sodium and the mechanism of hyponatremia-induced bone loss. J Biol Chem. 2011 Mar 25;286(12):10864-75. doi: 10.1074/jbc.M110.155002. Epub 2010 Dec 6.
citation: Himmerkus N, Sievers B, Bleich M. Carbamazepine affects water and electrolyte homoeostasis in rat--similarities and differences to vasopressin antagonism. Nephrol Dial Transplant. 2012 Oct;27(10):3790-8. doi: 10.1093/ndt/gfs107. Epub 2012 May 4.