ManiaPhase 3TRMNCT00518947
Pharmacotherapy of Treatment-Resistant Mania
A Phase 3 study testing Lithium, verapamil and verapamil plus lithium in people with Mania, run by University of Pittsburgh at 1 site in United States.
Trial summary
Verapamil has been found in some but not all studies to have antimanic activity. Therefore, we investigated the use of verapamil, alone or as an adjunctive treatment, in manic patients who did not respond to an initial adequate trial of lithium. Each study phase lasted three weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mania
- What is being tested?
- Lithium, verapamil and verapamil plus lithium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 1994to Jun 1999
- Phase
- Phase 3
- 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
- To be eligible for the study, patients were required to have a lifetime diagnosis of bipolar 1 or schizoaffective disorder, a current manic episode meeting DSM-IV criteria, and ratings >/= 7 on the Raskin Severity of Mania Scale and >/= 15 on the Bech-Rafaelsen Mania Scale.
Who cannot join
- Patients were excluded if they had:
- A pattern of severe rapid-cycling in which the patient consistently failed to meet the duration criteria for discreet episodes of syndromal mania or depression according to DSM-IV
- Sustained drug or alcohol abuse within the past three years
- Schizophrenia
- Organic affective syndrome
- A presenting episode that was secondary to the effect of any pharmacologic agent
Show all 9Show fewer
- The presence of significant medical illness that would preclude or unduly complicate the intended pharmacologic management of the episode
- In females, refusal to use appropriate contraception; or
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Verapamil has been found in some but not all studies to have antimanic activity. Therefore, we investigated the use of verapamil, alone or as an adjunctive treatment, in manic patients who did not respond to an initial adequate trial of lithium. Each study phase lasted three weeks. Subjects were treated openly with lithium in Phase 1 (n=45). Those who failed to respond were randomly assigned to double-blind treatment in Phase 2 with either verapamil (n=10) or continued lithium (n=8). Phase 2 responders were continued on the same medication in Phase 3. Phase 2 nonresponders (n=10) were assigned to combined verapamil/lithium in Phase 3.
- Conditions
- Mania
- Being tested
- Lithium, verapamil, verapamil plus lithium
- Keywords
- Bipolar Disorder, Mania, Antimanic, Verapamil, Lithium
- Medical subject headings
- Mania, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LithiumDrug
Treatment with lithium carbonate was initiated at a dose of 900-1200 mg/day. Serum lithium levels were monitored twice weekly, and the dose was adjusted to attain target levels between 0.8 and 1.0 mmol/L by the end of week one, with subsequent levels as high as 1.4 mmol/L permitted if needed.
verapamilDrug
The initial dose of verapamil was 80 mg b.i.d., and this was raised by 80 mg/day every three days to a maximum of 480 mg/day, unless intolerable side effects were produced at a lower level, in which case the dose was maintained at the highest tolerated amount.
verapamil plus lithiumDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Continued-Lithium Receives: Drug: Lithium |
| 2. | Experimental | Verapamil Receives: Drug: verapamil |
| 3. | Experimental | Verapamil plus Lithium Receives: Drug: verapamil plus lithium |
What is being measured
The primary outcome is the main question the study is designed to answer.
A > 50% reduction in Bech-Rafaelsen Mania Scale score (relative to the baseline score at the start of the phase), and, a total Bech-Rafaelsen Mania Scale score < 11
Measured: 3 weeks
Very much improved or much improved (compared to baseline) on the Clinical Global Impressions scale
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2007 (estimated)
- Study startNov 1994
- Study completionJun 1999
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 ManiaStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Investigators
- Alan G. Mallinger, M.D., Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00518947
- Sponsor's protocol ID
- 1R01MH050634
- Acronym
- TRM
- Status last verified
- Feb 2011
- First submitted
- 8 Aug 2007
- Last updated
- 25 Feb 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Frank E, Kupfer DJ, Gerebtzoff A, Meya U, Laghrissi-Thode F, Grochocinski VJ, Houck PR, Mallinger AG, Gibbons RD. The development of study exit criteria for evaluating antimanic compounds. J Clin Psychiatry. 2001 Jun;62(6):421-5. doi: 10.4088/jcp.v62n0604.
PubMed 11465518Mallinger AG, Thase ME, Haskett R, Buttenfield J, Luckenbaugh DA, Frank E, Kupfer DJ, Manji HK. Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone: preliminary findings and a discussion of therapeutic mechanisms. Bipolar Disord. 2008 Dec;10(8):856-66. doi: 10.1111/j.1399-5618.2008.00636.x.
PubMed 19594501
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacotherapy of Treatment-Resistant Mania
- ClinicalTrials.gov ID
- NCT00518947
- Acronym / sponsor ID
- TRM / 1R01MH050634
- Conditions
- Mania
- Keywords
- Bipolar Disorder, Mania, Antimanic, Verapamil, Lithium
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Nov 1994
- Study completion
- Jun 1999 (actual)
- First posted
- 21 Aug 2007 (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.
Verapamil has been found in some but not all studies to have antimanic activity. Therefore, we investigated the use of verapamil, alone or as an adjunctive treatment, in manic patients who did not respond to an initial adequate trial of lithium. Each study phase lasted three weeks. Subjects were treated openly with lithium in Phase 1 (n=45). Those who failed to respond were randomly assigned to double-blind treatment in Phase 2 with either verapamil (n=10) or continued lithium (n=8). Phase 2 responders were continued on the same medication in Phase 3. Phase 2 nonresponders (n=10) were assigned to combined verapamil/lithium in Phase 3.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: LithiumContinued-Lithium |
| 2. | Experimental | Drug: verapamilVerapamil |
| 3. | Experimental | Drug: verapamil plus lithiumVerapamil plus Lithium |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- To be eligible for the study, patients were required to have a lifetime diagnosis of bipolar 1 or schizoaffective disorder, a current manic episode meeting DSM-IV criteria, and ratings >/= 7 on the Raskin Severity of Mania Scale and >/= 15 on the Bech-Rafaelsen Mania Scale.
Key exclusion criteria (9 listed)
- A pattern of severe rapid-cycling in which the patient consistently failed to meet the duration criteria for discreet episodes of syndromal mania or depression according to DSM-IV
- Sustained drug or alcohol abuse within the past three years
- Schizophrenia
- Organic affective syndrome
- A presenting episode that was secondary to the effect of any pharmacologic agent
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 |
|---|---|---|
| LithiumTreatment with lithium carbonate was initiated at a dose of 900-1200 mg/day. Serum lithium levels were monitored twice weekly, and the dose was adjusted to attain target levels between 0.8 and 1.0 mmol/L by the end of week one, with subsequent levels as high as 1.4 mmol/L permitted if needed. | Drug | 1 |
| verapamilThe initial dose of verapamil was 80 mg b.i.d., and this was raised by 80 mg/day every three days to a maximum of 480 mg/day, unless intolerable side effects were produced at a lower level, in which case the dose was maintained at the highest tolerated amount. | Drug | 2. |
| verapamil plus lithium | Drug | 3. |
Primary outcome
A > 50% reduction in Bech-Rafaelsen Mania Scale score (relative to the baseline score at the start of the phase), and, a total Bech-Rafaelsen Mania Scale score < 11
Time frame: 3 weeks
Very much improved or much improved (compared to baseline) on the Clinical Global Impressions scale
Time frame: 3 weeks
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 25 Feb 2011.
- Background: PubMed 11465518Frank E, Kupfer DJ, Gerebtzoff A, Meya U, Laghrissi-Thode F, Grochocinski VJ, Houck PR, Mallinger AG, Gibbons RD. The development of study exit criteria for evaluating antimanic compounds. J Clin Psychiatry. 2001 Jun;62(6):421-5. doi: 10.4088/jcp.v62n0604.
- Results publication: PubMed 19594501Mallinger AG, Thase ME, Haskett R, Buttenfield J, Luckenbaugh DA, Frank E, Kupfer DJ, Manji HK. Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone: preliminary findings and a discussion of therapeutic mechanisms. Bipolar Disord. 2008 Dec;10(8):856-66. doi: 10.1111/j.1399-5618.2008.00636.x.
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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.
Alan G. Mallinger, M.D. principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lithium, verapamil and verapamil plus lithium in people with Mania, run by University of Pittsburgh 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 1 inclusion and 9 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 25 Feb 2011. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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.
What does the primary outcome measure?
A > 50% reduction in Bech-Rafaelsen Mania Scale score (relative to the baseline score at the start of the phase), and, a total Bech-Rafaelsen Mania Scale score < 11 (time frame: 3 weeks). The study lists 2 primary outcomes in all. 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 NCT00518947, 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 25 Feb 2011.