Bipolar DisorderPhase 2/3NCT01528839
Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression
A Phase 2/3 study testing L-Thyroxine in people with Bipolar Disorder, run by Charite University, Berlin, Germany at 5 sites in 2 countries.
Trial summary
There is growing evidence that thyroid axis dysfunction may contribute to the pathophysiology of bipolar illness. Open-label studies have consistently demonstrated that the behavioral expression of bipolar disorder can be modified by a change in thyroid status, and in many instances the course of illness is improved… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- L-Thyroxine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Mar 2004to Aug 2008
- Phase
- Phase 2/3
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of bipolar I or II disorder, currently depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
- Hamilton Rating Scale for Depression (HAM-D) 17-item score ≥14, a HAM-D item 1 (depressed mood) score ≥2 at the screening and randomization visits
- Young Mania Rating Scale (YMRS) score ≤12 at the screening and randomization visits.
- Pretreatment with a mood stabilizer and/or an antidepressant at standard doses (Bauer et al. 2007a) for at least six weeks since the last dose adjustment, and for at least two weeks before enrollment
- Serum levels of mood stabilizer were required to be within therapeutic ranges
- TSH levels in normal range (serum TSH 0.3 - 4.7 mU/l)
Who cannot join
- Any axis I disorder other than bipolar disorder
- Recent ultra-rapid cycling course (12 or more episodes in previous year), - - a diagnosis of substance dependence (DSM-IV) or substance use (except for nicotine) within 12 months before the screening visit
- Clinically significant medical illness, especially severe cardiovascular diseases
- Organic brain disorder
- Current serious suicidal or homicidal risk by clinical judgment of the investigator
- History of previous or current thyroid disease
- Thyroid hormone treatment
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Germany4 sites
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
Berlin
Department of Psychiatry, LWL University Hospital, Ruhr University Bochum, Bochum, Germany
Bochum
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Dresden
Department of Psychiatry and Psychotherapy, University of Göttingen, Germany
Göttingen
United States1 site
University of California in Los Angeles
Los Angeles, California
About this study
Official title: Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression: A Multicenter, Randomized, Double-blind, Placebo-controlled Study.
There is growing evidence that thyroid axis dysfunction may contribute to the pathophysiology of bipolar illness. Open-label studies have consistently demonstrated that the behavioral expression of bipolar disorder can be modified by a change in thyroid status, and in many instances the course of illness is improved through the use of adjunct thyroid hormone treatment. Recent evidence emerged from acute intervention studies that add-on treatment with supraphysiological doses of levothyroxine is an effective augmenting agent in patients with a major depressive episode. The primary goal of this international multicenter trial (5 sites) is to determine in a 13-week, randomized, placebo-controlled design (1 week single-blind placebo run-in, 6 week double-blind, 6 week open-label) the efficacy and safety of add-on treatment with levothyroxine (300 mcg/d) in combination with mood stabilizer/antidepressant therapy in the treatment of patients with bipolar depression. The main hypotheses is: treatment with levothyroxine will result in a significantly greater mean reduction of HRSD total score and in a higher number of responders and remitters compared to placebo treatment. This proposal will build on our pilot data and provide evidence for the use of levothyroxine as an effective augmentation strategy in the treatment of bipolar depression.
- Conditions
- Bipolar Disorder
- Being tested
- L-Thyroxine, Placebo
- Keywords
- Bipolar disorder, Bipolar depression, Thyroid abnormality, mood stabilizer, antidepressants, currently depressed
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-ThyroxineDrug
L-Thyroxine as addon to ongoing stable antidepressant and /or mood stabilizing therapy: week 1: 100 mcg; week 2: 200 mcg: week 3 to week 6: 300 mcg
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Pill | Placebo comparator | Not described Receives: Drug: Placebo |
| L-Thyroxine as addon | Experimental | Not described Receives: Drug: L-Thyroxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change in Hamilton Rating Scale for Depression (HRSD, 17 items)
Measured: baseline and six weeks
Secondary outcomes (2)
Mean change and single items change in the Thyroid Symtom List (TSL)
Measured: baseline and six weeks
Remission/Response
Rate of Resonders (>50% decline in HRDS) and Remitters (HRDS- score < 9)after l-Thyroxine addon treatment
Measured: six weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2012 (estimated)
- Study startMar 2004
- Primary completionMay 2008
- Study completionAug 2008
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 Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Responsible party
- Principal investigator, Thomas Stamm, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01528839
- Sponsor's protocol ID
- 1908Si267
- Status last verified
- Feb 2012
- First submitted
- 6 Feb 2012
- Last updated
- 8 Feb 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pilhatsch M, J Stamm T, Stahl P, Lewitzka U, Berghofer A, Sauer C, Gitlin M, Frye MA, Whybrow PC, Bauer M. Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms. Int J Bipolar Disord. 2019 Oct 4;7(1):21. doi: 10.1186/s40345-019-0155-y.
PubMed 31583561Stamm TJ, Lewitzka U, Sauer C, Pilhatsch M, Smolka MN, Koeberle U, Adli M, Ricken R, Scherk H, Frye MA, Juckel G, Assion HJ, Gitlin M, Whybrow PC, Bauer M. Supraphysiologic doses of levothyroxine as adjunctive therapy in bipolar depression: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014 Feb;75(2):162-8. doi: 10.4088/JCP.12m08305.
PubMed 24345793
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression: A Multicenter, Randomized, Double-blind, Placebo-controlled Study.
- ClinicalTrials.gov ID
- NCT01528839
- Acronym / sponsor ID
- 1908Si267
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar disorder, Bipolar depression, Thyroid abnormality, mood stabilizer, antidepressants, currently depressed
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Study start
- Mar 2004
- Primary completion
- May 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 8 Feb 2012 (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.
There is growing evidence that thyroid axis dysfunction may contribute to the pathophysiology of bipolar illness. Open-label studies have consistently demonstrated that the behavioral expression of bipolar disorder can be modified by a change in thyroid status, and in many instances the course of illness is improved through the use of adjunct thyroid hormone treatment. Recent evidence emerged from acute intervention studies that add-on treatment with supraphysiological doses of levothyroxine is an effective augmenting agent in patients with a major depressive episode. The primary goal of this international multicenter trial (5 sites) is to determine in a 13-week, randomized, placebo-controlled design (1 week single-blind placebo run-in, 6 week double-blind, 6 week open-label) the efficacy and safety of add-on treatment with levothyroxine (300 mcg/d) in combination with mood stabilizer/antidepressant therapy in the treatment of patients with bipolar depression. The main hypotheses is: treatment with levothyroxine will result in a significantly greater mean reduction of HRSD total score and in a higher number of responders and remitters compared to placebo treatment. This proposal will build on our pilot data and provide evidence for the use of levothyroxine as an effective augmentation strategy in the treatment of bipolar depression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pill | Placebo comparator | Drug: Placebo |
| L-Thyroxine as addon | Experimental | Drug: L-Thyroxine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of bipolar I or II disorder, currently depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
- Hamilton Rating Scale for Depression (HAM-D) 17-item score ≥14, a HAM-D item 1 (depressed mood) score ≥2 at the screening and randomization visits
- Young Mania Rating Scale (YMRS) score ≤12 at the screening and randomization visits.
- Pretreatment with a mood stabilizer and/or an antidepressant at standard doses (Bauer et al. 2007a) for at least six weeks since the last dose adjustment, and for at least two weeks before enrollment
- Serum levels of mood stabilizer were required to be within therapeutic ranges
Key exclusion criteria (7 listed)
- Any axis I disorder other than bipolar disorder
- Recent ultra-rapid cycling course (12 or more episodes in previous year), - - a diagnosis of substance dependence (DSM-IV) or substance use (except for nicotine) within 12 months before the screening visit
- Clinically significant medical illness, especially severe cardiovascular diseases
- Organic brain disorder
- Current serious suicidal or homicidal risk by clinical judgment of the investigator
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 |
|---|---|---|
| L-ThyroxineL-Thyroxine as addon to ongoing stable antidepressant and /or mood stabilizing therapy: week 1: 100 mcg; week 2: 200 mcg: week 3 to week 6: 300 mcg | Drug | L-Thyroxine as addon |
| Placebo | Drug | Pill |
Primary outcome
Mean change in Hamilton Rating Scale for Depression (HRSD, 17 items)
Time frame: baseline and six weeks
2 secondary outcomes
Mean change and single items change in the Thyroid Symtom List (TSL)
Time frame: baseline and six weeks
Remission/Response
Time frame: six 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 8 Feb 2012.
- Derived from this study: PubMed 31583561Pilhatsch M, J Stamm T, Stahl P, Lewitzka U, Berghofer A, Sauer C, Gitlin M, Frye MA, Whybrow PC, Bauer M. Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms. Int J Bipolar Disord. 2019 Oct 4;7(1):21. doi: 10.1186/s40345-019-0155-y.
- Derived from this study: PubMed 24345793Stamm TJ, Lewitzka U, Sauer C, Pilhatsch M, Smolka MN, Koeberle U, Adli M, Ricken R, Scherk H, Frye MA, Juckel G, Assion HJ, Gitlin M, Whybrow PC, Bauer M. Supraphysiologic doses of levothyroxine as adjunctive therapy in bipolar depression: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014 Feb;75(2):162-8. doi: 10.4088/JCP.12m08305.
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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.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing L-Thyroxine in people with Bipolar Disorder, run by Charite University, Berlin, Germany at 5 sites in 2 countries.
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 7 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 8 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany, 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
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?
Mean change in Hamilton Rating Scale for Depression (HRSD, 17 items) (time frame: baseline and six weeks). 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 NCT01528839, 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 8 Feb 2012.