Bipolar DisorderPhase 2NCT00015769
Pilot Study of Levetiracetam (Keppra® (Registered Trademark)) for Bipolar Illness
A Phase 2 study testing levetiracetam in people with Bipolar Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study will explore the possible effectiveness of levetiracetam in patients with bipolar illness who have not responded adequately to standard treatments. Levetiracetam was recently approved to treat seizures. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- levetiracetam
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2001to Apr 2003
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients meeting DSM -IV criteria for bipolar I, bipolar II, bipolar NOS, and schizoaffective illness-bipolar type will be eligible for study. They will be enrolled in approved Protocol #97-M-0039 and thus will not have H.I.V. and will have provided consent for all of the rating forms utilized in this study.
- Patients with inadequate response to two standard agents (i.e., lithium, valproate, carbamazepine, or neuroleptics) in the treatment of bipolar illness will be eligible for open adjunctive levetiracetam.
- If serum creatinine is above normal, a creatinine clearance will be preformed; this must be above 85 in order for a patient to be eligible for this study.
Who cannot join
- Women of child-bearing age who are not on an active method of birth control or who are likely to become pregnant will be excluded.
- Men or women with significant renal disease will also be excluded.
- For the depressed phase, patients will have an IDS score of 18 or greater, an LCM depression score of low moderate or greater, and a GCI-BP severity score of moderate or greater for more than 2 weeks, i.e., the DSM-IV durational criteria.
- For the hypomanic/manic phase, patients will have an YMRS score of 8 or greater, an LCM mania rating of mild or greater, and a CGI-BP severity score of moderately ill or greater for 7 days or more.
- Those in the cycling group would meet the severity criteria for depression and mania. They would have four or more mood "switches," and have an overall illness rating on the CGI-BP severity score of moderate or greater.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Mental Health (NIMH)
Bethesda, Maryland, 20892
About this study
Official title: Pilot Evaluation of Levetiracetam (Keppra® (Registered Trademark)) in Bipolar Illness
This study will explore the possible effectiveness of levetiracetam in patients with bipolar illness who have not responded adequately to standard treatments. Levetiracetam was recently approved to treat seizures. Other drugs in the same class as levetiracetam, including carbamazepine and valproate, are widely recognized as substitute medications for lithium or are used as an adjunct to it, and other anticonvulsants have also shown promise in improving bipolar symptoms.
Patients with bipolar illness whose manic, depressed or unstable moods are not adequately controlled by their current treatment and who have not responded previously to two standard treatments (i.e., lithium, valproate, carbamazepine or neuroleptics) may be eligible for this study.
Participants will take levetiracetam starting at 500 mg daily. If this dose is well tolerated, it will be increased to 500 mg twice a day. Every 3 days, doses may be increased until the target dose of 3000 mg/day is reached. Higher doses, not to exceed 4000 mg/day, may be tried in patients who do not respond fully to the lower doses. Patients and observers will use standard ratings to evaluate the patients' response to therapy during the 8-week study. If, after 8 weeks, the results appear promising, patients may continue treatment for an additional 6 months to evaluate longer-term effects.
Read the detailed description
Almost all of the approved anticonvulsant compounds (with the exception of gabapentin and tiagabine) have now been suggested to have acute antimanic or more long-term mood stabilizing properties. Carbamazepine and valproate have gained a widely recognized role in treatment algorithms of bipolar illness, and lamotrigine has shown promising antidepressant effects. Levetiracetam (Keppra® (Registered Trademark)) is the most recently approved anti-epileptic drug available, and deserves pilot exploration in bipolar illness for a variety of reasons. These include: its positive side-effects profile; it is a derivative of the nootropic agent piracetam which has memory-enhancing properties in animal studies; it likely has a unique mechanism of action since it is not active on most of the traditional excitatory and inhibitory neurotransmitter systems; it is not active on traditional anticonvulsant models such as pentylenetetrazol (PTZ) or maximum electroshock (MES) seizures, but is able to stop both the development and completed phase of amygdala-kindled seizures; and it is not metabolized by hepatic enzymes and thus has few adverse pharmacokinetic interactions.
We propose pilot exploration of levetiracetam as an adjunctive agent in patients with bipolar illness who are inadequately responsive to routine psychopharmacological agents for bipolar illness. At the NIMH we will study a maximum of 10 acutely depressed, 10 manic, and 10 cycling patients enrolled in Protocol 97-M-0039. We would start at Levetiracetam doses of 500 mg/day, and not to exceed 4000 mg/day. Response will be based primarily on the percentage of patients showing "much" or "very much" improvement on the GCI-BP score in each of the three groups as augmented by the percentage decrement on cross-sectional scales such as the Inventory of Depressive Symptomatology (IDS) and Young Mania Rating Scale (YMRS) in conjunction with prospective ratings on the NIMH-LCMp. Should preliminary evidence of efficacy be observed in this open add-on clinical trial, more systematic controlled studies will then be designed for confirmation of promising target areas of efficacy.
- Conditions
- Bipolar Disorder
- Being tested
- levetiracetam
- Keywords
- Mania, Depression, Anticonvulsants, Mood Stabilizers, Bipolar, Mood Stabilizer
- Medical subject headings
- Bipolar Disorder, Mania, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
levetiracetamDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2001 (estimated)
- Study startApr 2001
- Study completionApr 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Enrolment
- 30 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00015769
- Sponsor's protocol ID
- 010168
- Other IDs
- 01-M-0168
- Status last verified
- Apr 2003
- First submitted
- 4 May 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Altshuler LL, Keck PE Jr, McElroy SL, Suppes T, Brown ES, Denicoff K, Frye M, Gitlin M, Hwang S, Goodman R, Leverich G, Nolen W, Kupka R, Post R. Gabapentin in the acute treatment of refractory bipolar disorder. Bipolar Disord. 1999 Sep;1(1):61-5. doi: 10.1034/j.1399-5618.1999.10113.x.
PubMed 11256659Denicoff KD, Smith-Jackson EE, Disney ER, Ali SO, Leverich GS, Post RM. Comparative prophylactic efficacy of lithium, carbamazepine, and the combination in bipolar disorder. J Clin Psychiatry. 1997 Nov;58(11):470-8. doi: 10.4088/jcp.v58n1102.
PubMed 9413412Calabrese JR, Rapport DJ, Shelton MD, Kujawa M, Kimmel SE. Clinical studies on the use of lamotrigine in bipolar disorder. Neuropsychobiology. 1998 Oct;38(3):185-91. doi: 10.1159/000026535.
PubMed 9778607
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Evaluation of Levetiracetam (Keppra® (Registered Trademark)) in Bipolar Illness
- ClinicalTrials.gov ID
- NCT00015769
- Acronym / sponsor ID
- 010168
- Conditions
- Bipolar Disorder
- Keywords
- Mania, Depression, Anticonvulsants, Mood Stabilizers, Bipolar, Mood Stabilizer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Apr 2001
- Study completion
- Apr 2003
- First posted
- 7 May 2001 (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.
This study will explore the possible effectiveness of levetiracetam in patients with bipolar illness who have not responded adequately to standard treatments. Levetiracetam was recently approved to treat seizures. Other drugs in the same class as levetiracetam, including carbamazepine and valproate, are widely recognized as substitute medications for lithium or are used as an adjunct to it, and other anticonvulsants have also shown promise in improving bipolar symptoms.
Patients with bipolar illness whose manic, depressed or unstable moods are not adequately controlled by their current treatment and who have not responded previously to two standard treatments (i.e., lithium, valproate, carbamazepine or neuroleptics) may be eligible for this study.
Participants will take levetiracetam starting at 500 mg daily. If this dose is well tolerated, it will be increased to 500 mg twice a day. Every 3 days, doses may be increased until the target dose of 3000 mg/day is reached. Higher doses, not to exceed 4000 mg/day, may be tried in patients who do not respond fully to the lower doses. Patients and observers will use standard ratings to evaluate the patients' response to therapy during the 8-week study. If, after 8 weeks, the results appear promising, patients may continue treatment for an additional 6 months to evaluate longer-term effects.
Detailed description
Almost all of the approved anticonvulsant compounds (with the exception of gabapentin and tiagabine) have now been suggested to have acute antimanic or more long-term mood stabilizing properties. Carbamazepine and valproate have gained a widely recognized role in treatment algorithms of bipolar illness, and lamotrigine has shown promising antidepressant effects. Levetiracetam (Keppra® (Registered Trademark)) is the most recently approved anti-epileptic drug available, and deserves pilot exploration in bipolar illness for a variety of reasons. These include: its positive side-effects profile; it is a derivative of the nootropic agent piracetam which has memory-enhancing properties in animal studies; it likely has a unique mechanism of action since it is not active on most of the traditional excitatory and inhibitory neurotransmitter systems; it is not active on traditional anticonvulsant models such as pentylenetetrazol (PTZ) or maximum electroshock (MES) seizures, but is able to stop both the development and completed phase of amygdala-kindled seizures; and it is not metabolized by hepatic enzymes and thus has few adverse pharmacokinetic interactions.
We propose pilot exploration of levetiracetam as an adjunctive agent in patients with bipolar illness who are inadequately responsive to routine psychopharmacological agents for bipolar illness. At the NIMH we will study a maximum of 10 acutely depressed, 10 manic, and 10 cycling patients enrolled in Protocol 97-M-0039. We would start at Levetiracetam doses of 500 mg/day, and not to exceed 4000 mg/day. Response will be based primarily on the percentage of patients showing "much" or "very much" improvement on the GCI-BP score in each of the three groups as augmented by the percentage decrement on cross-sectional scales such as the Inventory of Depressive Symptomatology (IDS) and Young Mania Rating Scale (YMRS) in conjunction with prospective ratings on the NIMH-LCMp. Should preliminary evidence of efficacy be observed in this open add-on clinical trial, more systematic controlled studies will then be designed for confirmation of promising target areas of efficacy.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Patients meeting DSM -IV criteria for bipolar I, bipolar II, bipolar NOS, and schizoaffective illness-bipolar type will be eligible for study. They will be enrolled in approved Protocol #97-M-0039 and thus will not have H.I.V. and will have provided consent for all of the rating forms utilized in this study.
- Patients with inadequate response to two standard agents (i.e., lithium, valproate, carbamazepine, or neuroleptics) in the treatment of bipolar illness will be eligible for open adjunctive levetiracetam.
- If serum creatinine is above normal, a creatinine clearance will be preformed; this must be above 85 in order for a patient to be eligible for this study.
Key exclusion criteria (5 listed)
- Women of child-bearing age who are not on an active method of birth control or who are likely to become pregnant will be excluded.
- Men or women with significant renal disease will also be excluded.
- For the depressed phase, patients will have an IDS score of 18 or greater, an LCM depression score of low moderate or greater, and a GCI-BP severity score of moderate or greater for more than 2 weeks, i.e., the DSM-IV durational criteria.
- For the hypomanic/manic phase, patients will have an YMRS score of 8 or greater, an LCM mania rating of mild or greater, and a CGI-BP severity score of moderately ill or greater for 7 days or more.
- Those in the cycling group would meet the severity criteria for depression and mania. They would have four or more mood "switches," and have an overall illness rating on the CGI-BP severity score of moderate or greater.
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 |
|---|---|---|
| levetiracetam | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 11256659Altshuler LL, Keck PE Jr, McElroy SL, Suppes T, Brown ES, Denicoff K, Frye M, Gitlin M, Hwang S, Goodman R, Leverich G, Nolen W, Kupka R, Post R. Gabapentin in the acute treatment of refractory bipolar disorder. Bipolar Disord. 1999 Sep;1(1):61-5. doi: 10.1034/j.1399-5618.1999.10113.x.
- Background: PubMed 9413412Denicoff KD, Smith-Jackson EE, Disney ER, Ali SO, Leverich GS, Post RM. Comparative prophylactic efficacy of lithium, carbamazepine, and the combination in bipolar disorder. J Clin Psychiatry. 1997 Nov;58(11):470-8. doi: 10.4088/jcp.v58n1102.
- Background: PubMed 9778607Calabrese JR, Rapport DJ, Shelton MD, Kujawa M, Kimmel SE. Clinical studies on the use of lamotrigine in bipolar disorder. Neuropsychobiology. 1998 Oct;38(3):185-91. doi: 10.1159/000026535.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing levetiracetam in people with Bipolar Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
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 3 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: finished, as of the sponsor's last update on 4 Mar 2008. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00015769, which also lists 3 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 4 Mar 2008.