DepressionPhase 4LASTNCT00927550
Lithium and Standard Therapy in Resistant Depression
A Phase 4 study testing lithium in people with Depression, run by Universita di Verona at 1 site in Italy.
Trial summary
The principal clinical question is whether lithium is effective in reducing the risk of suicidal behaviour in subjects with treatment-resistant depression and suicide risk. Additionally aims of the study are: (a) to assess whether lithium is effective in improving depressive symptomatology in subjects with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depression
- What is being tested?
- lithium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2009to Dec 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of major depression (clinical diagnosis, guided by DSM-IV criteria).
- History of attempted suicide or deliberate self-harm in the previous 12 months.
- Inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode.
- Uncertainty about which treatment arm would be best for participant.
- Age 18 or above.
- Agreement between investigator and patient to enter the study.
Who cannot join
- In addition to major depression, a primary diagnosis of any concurrent Axis I disorder (according to DSM-IV criteria) will constitute an exclusion criterion; by contrast, any concurrent Axis II disorder (according to DSM-IV criteria) will not constitute an exclusion criterion.
- Previous exposure to lithium was associated with lack of efficacy or unwanted adverse reactions.
- Clinical conditions contraindicate the experimental treatment arm (for example thyroid or kidney disease or abnormalities).
- Pregnant/lactating women.
- Women of childbearing potential not practicing a reliable method of contraception.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
University of Verona
Verona, 37134
Corrado Barbui, MD, corrado.barbui@univr.it
Andrea Cipriani, MD
About this study
Official title: Randomized Evaluation of the Effectiveness of Lithium in Subjects With Treatment-Resistant Depression and Suicide Risk. An Independent, Pragmatic, Multicentre, Parallel-Group, Superiority Trial
The principal clinical question is whether lithium is effective in reducing the risk of suicidal behaviour in subjects with treatment-resistant depression and suicide risk. Additionally aims of the study are: (a) to assess whether lithium is effective in improving depressive symptomatology in subjects with treatment-resistant depression and suicide risk; (b) to assess the tolerability profile of lithium.
Read the detailed description
Inclusion criteria:
- Diagnosis of major depression (clinical diagnosis, guided by DSM-IV criteria).
- History of attempted suicide or deliberate self-harm in the previous 12 months.
- Inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode.
- Uncertainty about which treatment arm would be best for the participant.
- Age 18 or above.
- Agreement between investigator and patient to enter the study.
Exclusion criteria:
- In addition to major depression, a primary diagnosis of any concurrent Axis I disorder (according to DSM-IV criteria) will constitute an exclusion criterion; by contrast, any concurrent Axis II disorder (according to DSM-IV criteria) will not constitute an exclusion criterion.
- Previous exposure to lithium was associated with lack of efficacy or unwanted adverse reactions.
- Clinical conditions contraindicate the experimental treatment arm (for example thyroid or kidney disease or abnormalities).
- Pregnant/lactating women.
- Women of childbearing potential not practicing a reliable method of contraception.
PRIMARY OUTCOME DEFINITION
Suicide completion and acts of deliberate self harm (DSH) will constitute the composite primary outcome. The term "suicide" is defined as an act with a fatal outcome, deliberately initiated and performed by the person with the knowledge or expectation of its fatal outcome.
DSH is defined as intentional self-poisoning or self-injury, irrespective of motivation. Self-poisoning includes the intentional self-ingestion of more than the prescribed amount of any drug, whether or not there is evidence that the act was intended to result in death. This also includes poisoning with non-ingestible substances and gas, overdoses of "recreational drugs" and severe alcohol intoxication where clinical staff consider such cases to be an act of intentional self-harm (rather than recreational binge drinking). Self-injury is defined as any injury that has been intentionally self-inflicted, including self-cutting. The intention to end life may be absent or present to a variable degree. Other terms used to describe this phenomenon are "attempted suicide" and "parasuicide". Some acts of DSH are characterised by high suicidal intent, meticulous planning (including precautions against being found out), and severe lethality of the method used. Other acts of DSH are characterised by no or low intention of suicide, lack of planning and concealing of the act, and low lethality of the method used.
- Conditions
- Depression
- Being tested
- lithium, usual care
- Keywords
- resistant depression, lithium, RCT, lithium therapy, standard therapy
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lithiumDrug
Also called Carbolithium
Patients allocated to lithium will be administered an oral starting dose ranging between 150 and 300 milligrams. Suggested final oral dose will have to achieve plasma levels of 0.4 to 1.0 mmol/L. Clinicians will be free of increasing or decreasing the dose according to clinical status and circumstances. Dose changes will be recorded. Following randomization, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Patients allocated to the lithium arm will receive usual pharmacological and non-pharmacological treatment as clinically indicated. Any other pharmacological treatment will be allowed.
usual careDrug
Patients allocated to the control arm will receive usual pharmacological and non-pharmacological treatment as clinically indicated. Patients allocated to the control arm will not be allowed to receive lithium. Any other pharmacological treatment will be allowed.
| Study group | Role | What they receive |
|---|---|---|
| lithium plus usual care | Experimental | Not described Receives: Drug: lithium |
| usual care without lithium therapy | Active comparator | Not described Receives: Drug: usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Suicide completion and acts of deliberate self harm (DSH) will constitute the composite primary outcome
Measured: One year
Secondary outcomes (5)
All-cause mortality
Measured: One year
Suicide mortality
Measured: One year
Deliberate self-harm or attempted suicide
Measured: One year
Change in severity of depressive symptoms from baseline
Measured: One year
Adverse reactions during the study
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2009 (estimated)
- Study startJun 2009
- Primary completionDec 2012 (estimated)
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universita di Verona
- Sponsor type
- University, hospital or other
- Investigators
- Michele Tansella, MD, Professor of psychiatry, Study chair, Universita di Verona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00927550
- Sponsor's protocol ID
- LAST_RD_FARM77Z3BL-5.1_132009
- Acronym
- LAST
- Status last verified
- Sep 2009
- First submitted
- 24 Jun 2009
- Last updated
- 17 Sep 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Girlanda F, Cipriani A, Agrimi E, Appino MG, Barichello A, Beneduce R, Bighelli I, Bisoffi G, Bisogno A, Bortolaso P, Boso M, Calandra C, Cascone L, Castellazzi M, Corbascio C, Parise VF, Gardellin F, Gennaro D, Hanife B, Lintas C, Lorusso M, Luca A, Luca M, Luchetta C, Lucii C, Maio F, Marsilio A, Mattei C, Moretti D, Nose M, Occhionero G, Papanti D, Pecile D, Percudani M, Prestia D, Purgato M, Restaino F, Romeo S, Sciarma T, Strizzolo S, Tamborini S, Todarello O, Tozzi F, Ziero S, Zotos S, Barbui C. Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial. BMC Res Notes. 2014 Oct 17;7:731. doi: 10.1186/1756-0500-7-731.
PubMed 25326163Cipriani A, Girlanda F, Agrimi E, Barichello A, Beneduce R, Bighelli I, Bisoffi G, Bisogno A, Bortolaso P, Boso M, Calandra C, Cascone L, Corbascio C, Parise VF, Gardellin F, Gennaro D, Hanife B, Lintas C, Lorusso M, Luchetta C, Lucii C, Cernuto F, Tozzi F, Marsilio A, Maio F, Mattei C, Moretti D, Appino MG, Nose M, Occhionero G, Papanti D, Pecile D, Purgato M, Prestia D, Restaino F, Sciarma T, Ruberto A, Strizzolo S, Tamborini S, Todarello O, Ziero S, Zotos S, Barbui C. Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial. BMC Psychiatry. 2013 Aug 13;13:212. doi: 10.1186/1471-244X-13-212.
PubMed 23941474
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Evaluation of the Effectiveness of Lithium in Subjects With Treatment-Resistant Depression and Suicide Risk. An Independent, Pragmatic, Multicentre, Parallel-Group, Superiority Trial
- ClinicalTrials.gov ID
- NCT00927550
- Acronym / sponsor ID
- LAST / LAST_RD_FARM77Z3BL-5.1_132009
- Conditions
- Depression
- Keywords
- resistant depression, lithium, RCT, lithium therapy, standard therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 230 participants (estimated)
- Lead sponsor
- Universita di VeronaUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 25 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The principal clinical question is whether lithium is effective in reducing the risk of suicidal behaviour in subjects with treatment-resistant depression and suicide risk. Additionally aims of the study are: (a) to assess whether lithium is effective in improving depressive symptomatology in subjects with treatment-resistant depression and suicide risk; (b) to assess the tolerability profile of lithium.
Detailed description
Inclusion criteria:
- Diagnosis of major depression (clinical diagnosis, guided by DSM-IV criteria).
- History of attempted suicide or deliberate self-harm in the previous 12 months.
- Inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode.
- Uncertainty about which treatment arm would be best for the participant.
- Age 18 or above.
- Agreement between investigator and patient to enter the study.
Exclusion criteria:
- In addition to major depression, a primary diagnosis of any concurrent Axis I disorder (according to DSM-IV criteria) will constitute an exclusion criterion; by contrast, any concurrent Axis II disorder (according to DSM-IV criteria) will not constitute an exclusion criterion.
- Previous exposure to lithium was associated with lack of efficacy or unwanted adverse reactions.
- Clinical conditions contraindicate the experimental treatment arm (for example thyroid or kidney disease or abnormalities).
- Pregnant/lactating women.
- Women of childbearing potential not practicing a reliable method of contraception.
PRIMARY OUTCOME DEFINITION
Suicide completion and acts of deliberate self harm (DSH) will constitute the composite primary outcome. The term "suicide" is defined as an act with a fatal outcome, deliberately initiated and performed by the person with the knowledge or expectation of its fatal outcome.
DSH is defined as intentional self-poisoning or self-injury, irrespective of motivation. Self-poisoning includes the intentional self-ingestion of more than the prescribed amount of any drug, whether or not there is evidence that the act was intended to result in death. This also includes poisoning with non-ingestible substances and gas, overdoses of "recreational drugs" and severe alcohol intoxication where clinical staff consider such cases to be an act of intentional self-harm (rather than recreational binge drinking). Self-injury is defined as any injury that has been intentionally self-inflicted, including self-cutting. The intention to end life may be absent or present to a variable degree. Other terms used to describe this phenomenon are "attempted suicide" and "parasuicide". Some acts of DSH are characterised by high suicidal intent, meticulous planning (including precautions against being found out), and severe lethality of the method used. Other acts of DSH are characterised by no or low intention of suicide, lack of planning and concealing of the act, and low lethality of the method used.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| lithium plus usual care | Experimental | Drug: lithium |
| usual care without lithium therapy | Active comparator | Drug: usual care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of major depression (clinical diagnosis, guided by DSM-IV criteria).
- History of attempted suicide or deliberate self-harm in the previous 12 months.
- Inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode.
- Uncertainty about which treatment arm would be best for participant.
- Age 18 or above.
Key exclusion criteria (5 listed)
- In addition to major depression, a primary diagnosis of any concurrent Axis I disorder (according to DSM-IV criteria) will constitute an exclusion criterion; by contrast, any concurrent Axis II disorder (according to DSM-IV criteria) will not constitute an exclusion criterion.
- Previous exposure to lithium was associated with lack of efficacy or unwanted adverse reactions.
- Clinical conditions contraindicate the experimental treatment arm (for example thyroid or kidney disease or abnormalities).
- Pregnant/lactating women.
- Women of childbearing potential not practicing a reliable method of contraception.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lithiumAlso: CarbolithiumPatients allocated to lithium will be administered an oral starting dose ranging between 150 and 300 milligrams. Suggested final oral dose will have to achieve plasma levels of 0.4 to 1.0 mmol/L. Clinicians will be free of increasing or decreasing the dose according to clinical status and circumstances. Dose changes will be recorded. Following randomization, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Patients allocated to the lithium arm will receive usual pharmacological and non-pharmacological treatment as clinically indicated. Any other pharmacological treatment will be allowed. | Drug | lithium plus usual care |
| usual carePatients allocated to the control arm will receive usual pharmacological and non-pharmacological treatment as clinically indicated. Patients allocated to the control arm will not be allowed to receive lithium. Any other pharmacological treatment will be allowed. | Drug | usual care without lithium therapy |
Primary outcome
Suicide completion and acts of deliberate self harm (DSH) will constitute the composite primary outcome
Time frame: One year
5 secondary outcomes
All-cause mortality
Time frame: One year
Suicide mortality
Time frame: One year
Deliberate self-harm or attempted suicide
Time frame: One year
Change in severity of depressive symptoms from baseline
Time frame: One year
Adverse reactions during the study
Time frame: One year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2009.
- Derived from this study: PubMed 25326163Girlanda F, Cipriani A, Agrimi E, Appino MG, Barichello A, Beneduce R, Bighelli I, Bisoffi G, Bisogno A, Bortolaso P, Boso M, Calandra C, Cascone L, Castellazzi M, Corbascio C, Parise VF, Gardellin F, Gennaro D, Hanife B, Lintas C, Lorusso M, Luca A, Luca M, Luchetta C, Lucii C, Maio F, Marsilio A, Mattei C, Moretti D, Nose M, Occhionero G, Papanti D, Pecile D, Percudani M, Prestia D, Purgato M, Restaino F, Romeo S, Sciarma T, Strizzolo S, Tamborini S, Todarello O, Tozzi F, Ziero S, Zotos S, Barbui C. Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial. BMC Res Notes. 2014 Oct 17;7:731. doi: 10.1186/1756-0500-7-731.
- Derived from this study: PubMed 23941474Cipriani A, Girlanda F, Agrimi E, Barichello A, Beneduce R, Bighelli I, Bisoffi G, Bisogno A, Bortolaso P, Boso M, Calandra C, Cascone L, Corbascio C, Parise VF, Gardellin F, Gennaro D, Hanife B, Lintas C, Lorusso M, Luchetta C, Lucii C, Cernuto F, Tozzi F, Marsilio A, Maio F, Mattei C, Moretti D, Appino MG, Nose M, Occhionero G, Papanti D, Pecile D, Purgato M, Prestia D, Restaino F, Sciarma T, Ruberto A, Strizzolo S, Tamborini S, Todarello O, Ziero S, Zotos S, Barbui C. Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial. BMC Psychiatry. 2013 Aug 13;13:212. doi: 10.1186/1471-244X-13-212.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michele Tansella, MD, Professor of psychiatry study chair
Universita di Verona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing lithium in people with Depression, run by Universita di Verona at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact corrado barbui, MD (+39 0458126418, corrado.barbui@univr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Suicide completion and acts of deliberate self harm (DSH) will constitute the composite primary outcome (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00927550, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2009.