SALT Study (Switching to the Administration of Lithium Slow -Release Treatment)

Clinical Evaluation of Switching to Lithiofor® (Lithium Sulphate Slow -Release, Li-SR Tablets) From Carbolithium® (Lithium Carbonate Immediate-Release, Li-IR, Capsules) in Bipolar Patients, Poorly Tolerant to Lithium Immediate-release Treatment.

The aim of the study is to assess the tolerability, efficacy and safety of a new lithium sulphate prolonged release formulation (Lithiofor®) in patients affected by Bipolar Disorder poor tolerant to lithium immediate-release treatment in terms of lithium-induced tremor when switched from therapy with a lithium carbonate immediate release formulation (Carbolithium®) to a new lithium sulphate prolonged release formulation (Lithiofor®).

Study Overview

• Status: Terminated
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: Lithium sulphate prolonged-release 660 mg; Drug: Lithium carbonate immediate-release 150 mg and 300 mg

Detailed Description

This is a phase IV, randomized, open, parallel groups, multicentre, prospective study.

The main purpose of this clinical trial is to evaluate the change in the lithium induced tremor when switching from Lithium Immediate Release formulation (Carbolithium®) to Lithium Sulphate prolonged-release formulation (Lithiofor®) in Bipolar Disorder patients, poorly tolerant to the Lithium Immediate Release treatment. The primary end point will be the reduction of the lithium induced tremor.

Patients in treatment with lithium carbonate immediate-release (Carbolithium®), will be enrolled in the study and, after 1 week of maintaining treatment, will be randomly switched to Lithium prolonged-release formulation or will continue the previous therapy.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy, 24127
    • Azienda Ospedaliera Papa Giovanni XXIII - Servizio Psichiatrico di Diagnosi e Cura (SPDC 1)
  • Genova, Italy, 16132
    • IRCCS Azienda Ospedaliera Universitaria San Martino IST - Clinica Psichiatrica
  • Pisa, Italy, 56126
    • Azienda Ospedaliera Universitaria Pisana - Psichiatria 1
  • Roma, Italy, 00189
    • Azienda Ospedaliera Sant'Andrea - Dip. Di Neuroscienze, Salute mentale e Organi di senso- NESMOS
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese - Dip. Interaziendale di salute mentale - Psichiatria
  • Grosseto
    • Orbetello, Grosseto, Italy, 58016
      • Ospedale San Giovanni di Dio di Orbetello Unità Funzionale Salute Mentale

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients aged 18 to 65 years (limits included), with no limitation of race. Female patients with childbearing potential should have a negative pregnancy test and should not be breastfeeding. Male and female patients should use an appropriate birth control method.
2. Diagnosis of Bipolar disorder (BD) I or II (as per DSM-5), with or without rapid cycling.
3. BD patients in treatment with lithium Carbolithium® immediate-release, presenting at the screening and baseline low tolerability in terms of tremor (tremor severity assessment ≥ 2 on single item of the UKU side-effect rating scale).
4. MADRS score ≤ 10 and YMRS ≤ 12 at screening and baseline visits.
5. Patients legally capable to give the consent to participate in the study and available to sign and date the written informed consent.
6. Patient able to understand the study procedures and to comply with protocol requirements.

Exclusion Criteria:

1. Fulfilling criteria for the following disorders: schizophrenia, psychotic and schizoaffective disorders, unipolar depression; concomitant organic mental disorder or intellectual disability; history of dementia or cognitive disorders, any neurodegenerative diseases.
2. Known hypersensitivity or allergy to lithium or to any components of the study medications.
3. Pharmacological treatments affecting tremor, except for patients treated for at least 2 months before the screening visit (i.e. Beta-blockers; for further details).
4. Known tremor due to irreversible lithium neurotoxicity.
5. Patients at risk for suicidal behaviour.
6. Immunocompromised patients.
7. Acute, or chronic, or recurrent medical conditions that might affect/jeopardize the study results.
8. Significant liver disease, defined as known active hepatitis or elevated liver enzymes > 3 times the upper boundary of the normal ranges.
9. Value of creatinine outside the normal ranges and judged clinically relevant by Investigator.
10. Any contraindication listed in the Summaries of Product Characteristics (SmPC) of Carbolithium® and lithium sulphate prolonged-release tablets (Lithiofor®).
11. Positive history for drugs.
12. Alcohol abuse.
13. Positive urine drug screen for CNS-active drugs (cocaine, opioids, amphetamines and cannabinoids) at Visit 0 (screening).
14. Clinically significant abnormalities on physical examination, vital signs, ECG, laboratory tests prior to screening visit.
15. Inability to comply with the protocol requirements, instructions and study-related restrictions; e.g. uncooperative attitude, inability to return for study-visits, and improbability of completing the clinical study.
16. Vulnerable subjects (e.g. persons kept in detention).
17. Participation to an interventional clinical study within 3 months prior to the screening visit.
18. If Subject is the Investigator or his(her) deputies, first grade relative, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Lithium sulphate prolonged-release 660 mg	Drug: Lithium sulphate prolonged-release 660 mg; Oral administration of one tablet once or twice daily (one tablet in the morning and one tablet in the evening) or two tablets in a single dose (two tablets in the evening) of Lithium sulphate 660 mg (Lithium sulphate dose will be individualised for each patient according to the relevant SmPC). Treatment duration: 3 months.; Other Names: LITHIOFOR®
Active Comparator: Group 2; Lithium carbonate immediate-release 150 mg and 300 mg	Drug: Lithium carbonate immediate-release 150 mg and 300 mg; Oral administration of 300-1800 mg daily divided into 2-6 doses of Lithium carbonate capsules (Lithium carbonate dose will be individualised for each patient according to the relevant SmPC). Treatment duration: 3 months.; Other Names: CARBOLITHIUM®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of item 2.5 (tremor) in Udvalg for Kliniske Undersøgelser (UKU) scale	Proportion of patients with an improvement in tremor assessed by the change from baseline of item 2.5 in UKU side-effect rating scale after 1-week treatment period.	Baseline - Week 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of item 2.5 (tremor) in Udvalg for Kliniske Undersøgelser (UKU) scale	Proportion of patients with an improvement in tremor assessed by the change from baseline of item 2.5 in UKU side-effect rating scale after 4- and 12-week treatment period.	Baseline - Weeks 4 and 12
Change of item 3.8 in Udvalg for Kliniske Undersøgelser (UKU) scale	Proportion of patients with a change from baseline of item 3.8 in UKU side-effect rating scale after 1-, 4- and 12-week treatment period.	Baseline - Weeks 1, 4 and 12
Change in Montgomery-Asberg Depression Rating Scale (MADRS)	Change from baseline of total score in MADRS scale after 1-, 4- and 12-week treatment period.	Baseline - Weeks 1, 4 and 12
Change in Young Mania Rating Scale (YMRS)	Change from baseline of total score in YMRS scale after 1-, 4- and 12-week treatment period.	Baseline - Weeks 1, 4 and 12
Change in Treatment Satisfaction Questionnaire for Medication (TSQM) scale	Change from baseline in each sub-scale of TSQM after 1- and 12-week treatment period.	Baseline - Weeks 1 and 12
Change in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF)	Change from baseline in Q-LES-Q-SF after 1- and 12-week treatment period.	Baseline - Weeks 1 and 12
Change in Clinical Global Impression (CGI) scale	Assessment by the physician of the overall efficacy by CGI scale after 1- and 12-week treatment period.	Baseline - Weeks 1 and 12
Frequency of treatment-related adverse events	Monitoring of the frequency of adverse events, physical examination, vital signs, ECG, laboratory analyses, plasma Lithium concentration.	12 weeks

Collaborators and Investigators

• Sponsor: Aziende Chimiche Riunite Angelini Francesco S.p.A
• Collaborators: Mediolanum Cardio Research

Publications and helpful links

Helpful Links

• Sponsor website

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2017
• Primary Completion (Actual): September 20, 2019
• Study Completion (Actual): September 20, 2019

Study Registration Dates

• First Submitted: June 23, 2017
• First Submitted That Met QC Criteria: July 6, 2017
• First Posted (Actual): July 7, 2017

Study Record Updates

• Last Update Posted (Actual): January 10, 2020
• Last Update Submitted That Met QC Criteria: January 7, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Bipolar Disorder; Tremor; Lithium carbonate; Lithium Sulphate; Prolonged release formulation; Immediate release formulation
• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antimanic Agents; Lithium Carbonate
• Other Study ID Numbers: 136PO15274; 2016-001714-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No