Effect of Regulated Add -on Sodium Chloride Intake on Stabilization of Serum Lithium Concentration in Bipolar Disorder

Bipolar Affective Disorder Clinical Trial

Official title:

Effect of Regulated Add -on Sodium Chloride Intake on Stabilization of Serum Lithium Concentration in Bipolar Disorder: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04222816
• Other study ID #: IEC/AIIMS BBSR/PG Th/19-20/76
• Status: Completed
• Phase: Phase 4
• Start date: January 16, 2020
• Est. completion date: January 7, 2022

Study information

• Verified date: January 2022
• Source: All India Institute of Medical Sciences, Bhubaneswar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Bipolar affective disorder or manic -depressive psychosis (MDP) is a mood disorder affecting 2.4% of the global population . Lithium is considered as the "gold standard" for the treatment of bipolar disorder but the clinical use of lithium is often restricted due to its narrow therapeutic range and adverse effects.

In a published case report, Bleiwiss H found that sodium chloride supplementation diminished the adverse effects caused by lithium The literature search also revealed that till date, there is no published clinical study evaluating the effect of dietary intake of sodium in preventing the fluctuations of serum lithium level and lithium toxicity Therefore, a randomized clinical trial has been designed to evaluate the effect of regulated add -on dietary sodium chloride on serum lithium levels in bipolar disorder.

Description:

Bipolar affective disorder or manic -depressive psychosis (MDP) is a mood disorder affecting 2.4% of the global population. Lithium is considered as the "gold standard" for the treatment of bipolar disorder but the clinical use of lithium is often restricted due to its narrow therapeutic range and adverse effects.One of the major adverse effects of lithium is nephrogenic diabetes insipidus which is due to long -term renal dysfunction.

In the initial months of lithium therapy, psychiatrists face difficulty in titrating the dose and stabilizing serum lithium level and this fluctuation of serum lithium level may be due to a lithium-induced sodium depleted state.

In a published case report, Bleiwiss H found that sodium chloride supplementation diminished the adverse effects caused by lithium. 8 In another case report, Tomita et al demonstrated that the change in sodium chloride intake can bring about changes in serum lithium and help in stabilizing the levels of serum lithium concentration.

As all the case reports are from abroad, the effect of dietary sodium on serum lithium level among Indian population is completely unknown. The literature search also revealed that till date, there is no published clinical study evaluating the effect of dietary intake of sodium in preventing the fluctuations of serum lithium level and lithium toxicity. Therefore, a randomized clinical trial has been designed to evaluate the effect of regulated add -on dietary sodium chloride on serum lithium levels in bipolar disorder. This study may help to explore the role of add -on sodium chloride in decreasing the fluctuations in the serum lithium level and improving the clinical outcome of patients with bipolar disorders.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: January 7, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients aged 18 -60 years, of either sex with the clinical diagnosis of bipolar disorder (DSM V) who are on maintenance lithium therapy for = 1month and = 6 months.

• Patients with normal serum sodium level (135 -145 mEq/L) and serum lithium in the optimum therapeutic range (<0.6 mEq/ L or >0.8 mEq/ L) .

Exclusion Criteria:

• Patients with comorbidities like other psychiatric disorder s, organicity, substance abuse, personality disorder, intellectual disability and other neurotic disorders .

• Patients with any renal, cardiovascular, neurologica l, endocrinal and hepatic dysfunction.

• Patients suffering from diarrhoea, dehydration

• History of any invasive neurosurgical/ non -invasive neuropsychiatric procedure.

• Medication history of psychoactive or central nervous system depressant drugs.

• Patients who are on NSAIDs, ACE inhibitors, antiarrhythmics, diuretics and neuromuscular blocking agents .

• Pregnant and nursing women .

• Patients with drug/alcohol abuse.

Related Conditions & MeSH terms

• Bipolar Affective Disorder
• Bipolar Disorder
• Disease
• Mood Disorders

Intervention

Drug:
• Lithium Carbonate
Lithium carbonate 800-900 mg orally daily for 12 weeks
• Sodium chloride
Sodium chloride 1gm daily per orally for 12 weeks

Locations

Country	Name	City	State
India	Aiims Bhubaneswar	Khorda	Orissa

Sponsors (1)

Lead Sponsor	Collaborator
All India Institute of Medical Sciences, Bhubaneswar

Country where clinical trial is conducted

India, 

References & Publications (9)

Bleiweiss H. Salts supplements with lithium. Lancet. 1970 Feb 21;1(7643):416. — View Citation

Demers RG, Heninger GR. Sodium intake and lithium treatment in mania. Am J Psychiatry. 1971 Jul;128(1):100-4. — View Citation

Kessler RC, Ormel J, Petukhova M, McLaughlin KA, Green JG, Russo LJ, Stein DJ, Zaslavsky AM, Aguilar-Gaxiola S, Alonso J, Andrade L, Benjet C, de Girolamo G, de Graaf R, Demyttenaere K, Fayyad J, Haro JM, Hu Cy, Karam A, Lee S, Lepine JP, Matchsinger H, Mihaescu-Pintia C, Posada-Villa J, Sagar R, Ustün TB. Development of lifetime comorbidity in the World Health Organization world mental health surveys. Arch Gen Psychiatry. 2011 Jan;68(1):90-100. doi: 10.1001/archgenpsychiatry.2010.180. — View Citation

Mandal S, Mamidipalli SS, Mukherjee B, Hara SKH. Perspectives, attitude, and practice of lithium prescription among psychiatrists in India. Indian J Psychiatry. 2019 Sep-Oct;61(5):451-456. doi: 10.4103/psychiatry.IndianJPsychiatry_451_18. — View Citation

Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, Viana MC, Andrade LH, Hu C, Karam EG, Ladea M, Medina-Mora ME, Ono Y, Posada-Villa J, Sagar R, Wells JE, Zarkov Z. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011 Mar;68(3):241-51. doi: 10.1001/archgenpsychiatry.2011.12. — View Citation

Murthy RS. National Mental Health Survey of India 2015-2016. Indian J Psychiatry. 2017 Jan-Mar;59(1):21-26. doi: 10.4103/psychiatry.IndianJPsychiatry_102_17. — View Citation

Selvarajan S, Manohar H, Das S, Sakkarabani P, Kandasamy P. Lithium prophylaxis in early-onset Bipolar disorder: a descriptive study. Asian J Psychiatr. 2019 Aug;44:172-174. doi: 10.1016/j.ajp.2019.07.053. Epub 2019 Jul 30. — View Citation

Tomita T, Goto H, Sumiya K, Yoshida T, Tanaka K, Kohda Y. Stabilization of the Serum Lithium Concentration by Regulation of Sodium Chloride Intake: Case Report. Yakugaku Zasshi. 2016;136(3):517-21. doi: 10.1248/yakushi.15-00256. — View Citation

Tondo L, Vázquez GH, Baldessarini RJ. Depression and Mania in Bipolar Disorder. Curr Neuropharmacol. 2017 Apr;15(3):353-358. doi: 10.2174/1570159X14666160606210811. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in percentage of bipolar patients showing fluctuation in serum lithium level	Serum lithium level will be done by electrolyte analyzer. The patients showing fluctuations ( fluctuation is defined as serum lithium <0.6 mEq/ L or >0.8 mEq/ L in maintenance phase) in serum lithium level between the groups over 12 weeks.	12 weeks
Secondary	Serum sodium	Will be done by electrolyte analyzer.	12 weeks
Secondary	Serum Potassium	Will be done by electrolyte analyzer.	12 weeks
Secondary	Serum creatinine	Will be done by autoanalyser.	12 weeks
Secondary	Serum aldosterone	Will be done by commercially available ELISA kit.	12 weeks
Secondary	ECG changes	ECG changes for lithium toxicity (T wave inversion, PR prolongation, QT prolongation), hyponatremia (P wave alterations), hypernatremia (short PR interval and diffuse ST depression) will be looked for	12 weeks
Secondary	Serum Lithium	Will be done by electrolyte analyzer.	12 weeks