Clinical trial NCT03210480: SALT Study (Switching to the Administration of Lithium Slow -Release Treatment)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Bipolar Disorder
Keywords: Lithium Sulphate
Prolonged release formulation
Lithium carbonate
Immediate release formulation
Bipolar Disorder
Tremor
Lead sponsor: Aziende Chimiche Riunite Angelini Francesco S.p.A
Sponsor class: INDUSTRY
Collaborators: name: Mediolanum Cardio Research
First posted: 2017-07-07
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, multicenter, prospective study.
Primary purpose: TREATMENT

Brief summary: 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®).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change of item 2.5 (tremor) in Udvalg for Kliniske Undersøgelser (UKU) scale
timeFrame: Baseline - Week 1
Secondary outcomes:
measure: Change of item 2.5 (tremor) in Udvalg for Kliniske Undersøgelser (UKU) scale
timeFrame: Baseline - Weeks 4 and 12
measure: Change of item 3.8 in Udvalg for Kliniske Undersøgelser (UKU) scale
timeFrame: Baseline - Weeks 1, 4 and 12
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Baseline - Weeks 1, 4 and 12
measure: Change in Young Mania Rating Scale (YMRS)
timeFrame: Baseline - Weeks 1, 4 and 12
measure: Change in Treatment Satisfaction Questionnaire for Medication (TSQM) scale
timeFrame: Baseline - Weeks 1 and 12
measure: Change in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF)
timeFrame: Baseline - Weeks 1 and 12
measure: Change in Clinical Global Impression (CGI) scale
timeFrame: Baseline - Weeks 1 and 12
measure: Frequency of treatment-related adverse events
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Orbetello
country: Italy
facility: Ospedale San Giovanni di Dio di Orbetello Unità Funzionale Salute Mentale
state: Grosseto
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII - Servizio Psichiatrico di Diagnosi e Cura (SPDC 1)
city: Genova
country: Italy
facility: IRCCS Azienda Ospedaliera Universitaria San Martino IST - Clinica Psichiatrica
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana - Psichiatria 1
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea - Dip. Di Neuroscienze, Salute mentale e Organi di senso- NESMOS
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese - Dip. Interaziendale di salute mentale - Psichiatria
Study officials:
References: