Clinical trial NCT04222816: Effect of Regulated Add -on Sodium Chloride Intake on Stabilization of Serum Lithium Concentration in Bipolar Disorder
Official title: Effect of Regulated Add -on Sodium Chloride Intake on Stabilization of Serum Lithium Concentration in Bipolar Disorder: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Affective Disorder
Keywords: Bipolar affective disorder
Lithium
Manic depressive psychosis
Sodium chloride
Lead sponsor: All India Institute of Medical Sciences, Bhubaneswar
Sponsor class: OTHER
First posted: 2020-01-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, open label, parallel group, active controlled clinical trial
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Difference in percentage of bipolar patients showing fluctuation in serum lithium level
timeFrame: 12 weeks
Secondary outcomes:
measure: Serum sodium
timeFrame: 12 weeks
measure: Serum Potassium
timeFrame: 12 weeks
measure: Serum creatinine
timeFrame: 12 weeks
measure: Serum aldosterone
timeFrame: 12 weeks
measure: ECG changes
timeFrame: 12 weeks
measure: Serum Lithium
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Khorda
country: India
facility: Aiims Bhubaneswar
state: Orissa
Study officials:
affiliation: PROFESSOR AND HEAD OF THE DEPARTMENT
name: DEBASISH HOTA, DM
role: STUDY_DIRECTOR
References:
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.
citation: Bleiweiss H. Salts supplements with lithium. Lancet. 1970 Feb 21;1(7643):416. doi: 10.1016/s0140-6736(70)91550-3. No abstract available.
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.
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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, Ustun 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.
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