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

Sponsor

All India Institute of Medical Sciences, Bhubaneswar (Other)

Overall Status

Completed

CT.gov ID

NCT04222816

Collaborator

(none)

Enrollment

Location

Arms

23.7

Actual Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Affective Disorder	Drug: Lithium Carbonate Drug: Sodium chloride	Phase 4

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, open label, parallel group, active controlled clinical trialRandomized, open label, parallel group, active controlled clinical trial

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jan 16, 2020

Actual Primary Completion Date :

Dec 31, 2021

Actual Study Completion Date :

Jan 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lithium carbonate Lithium carbonate is prescribed 800-900 mg per day for 12 weeks.	Drug: Lithium Carbonate Lithium carbonate 800-900 mg orally daily for 12 weeks
Experimental: Add-on Sodium chloride Sodium chloride 1gm per day per will be prescribed along with Lithium carbonate 800-900 mg per day for 12 weeks.	Drug: Lithium Carbonate Lithium carbonate 800-900 mg orally daily for 12 weeks Drug: Sodium chloride Sodium chloride 1gm daily per orally for 12 weeks

Arm

Intervention/Treatment

Active Comparator: Lithium carbonate

Lithium carbonate is prescribed 800-900 mg per day for 12 weeks.

Drug: Lithium Carbonate

Lithium carbonate 800-900 mg orally daily for 12 weeks

Experimental: Add-on Sodium chloride

Sodium chloride 1gm per day per will be prescribed along with Lithium carbonate 800-900 mg per day for 12 weeks.

Drug: Lithium Carbonate

Lithium carbonate 800-900 mg orally daily for 12 weeks

Drug: Sodium chloride

Sodium chloride 1gm daily per orally for 12 weeks

Outcome Measures

Primary Outcome Measures

Difference in percentage of bipolar patients showing fluctuation in serum lithium level [12 weeks]
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.

Secondary Outcome Measures

Serum sodium [12 weeks]
Will be done by electrolyte analyzer.
Serum Potassium [12 weeks]
Will be done by electrolyte analyzer.
Serum creatinine [12 weeks]
Will be done by autoanalyser.
Serum aldosterone [12 weeks]
Will be done by commercially available ELISA kit.
ECG changes [12 weeks]
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
Serum Lithium [12 weeks]
Will be done by electrolyte analyzer.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.