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Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression

Primary Purpose

Bipolar Disorder

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

L-Thyroxine

Placebo

About this trial

This is an interventional treatment trial for Bipolar Disorder focused on measuring Bipolar disorder, Bipolar depression, Thyroid abnormality, mood stabilizer, antidepressants, currently depressed

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)

Exclusion Criteria:

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

Sites / Locations

University of California in Los Angeles
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
Department of Psychiatry, LWL University Hospital, Ruhr University Bochum, Bochum, Germany
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Department of Psychiatry and Psychotherapy, University of Göttingen, Germany

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Pill

L-Thyroxine as addon

Arm Description

Outcomes

Primary Outcome Measures

Mean change in Hamilton Rating Scale for Depression (HRSD, 17 items)

Secondary Outcome Measures

Mean change and single items change in the Thyroid Symtom List (TSL)

Remission/Response

Rate of Resonders (>50% decline in HRDS) and Remitters (HRDS- score < 9)after l-Thyroxine addon treatment

Full Information

NCT ID

NCT01528839

First Posted

February 6, 2012

Last Updated

February 7, 2012

Sponsor

Charite University, Berlin, Germany

Collaborators

Stanley Medical Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT01528839

Brief Title

Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression

Official Title

Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression: A Multicenter, Randomized, Double-blind, Placebo-controlled Study.

Study Type

Interventional

2. Study Status

Record Verification Date

February 2012

Overall Recruitment Status

Completed

Study Start Date

March 2004 (undefined)

Primary Completion Date

May 2008 (Actual)

Study Completion Date

August 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Charite University, Berlin, Germany

Collaborators

Stanley Medical Research Institute

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bipolar Disorder

Keywords

Bipolar disorder, Bipolar depression, Thyroid abnormality, mood stabilizer, antidepressants, currently depressed

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

74 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pill

Arm Type

Placebo Comparator

Arm Title

L-Thyroxine as addon

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

L-Thyroxine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Mean change in Hamilton Rating Scale for Depression (HRSD, 17 items)

Time Frame

baseline and six weeks

Secondary Outcome Measure Information:

Title

Mean change and single items change in the Thyroid Symtom List (TSL)

Time Frame

baseline and six weeks

Title

Remission/Response

Description

Rate of Resonders (>50% decline in HRDS) and Remitters (HRDS- score < 9)after l-Thyroxine addon treatment

Time Frame

six weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Exclusion Criteria: 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

Facility Information:

Facility Name

University of California in Los Angeles

City

Los Angeles

State/Province

California

Country

United States

Facility Name

Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany

City

Berlin

Country

Germany

Facility Name

Department of Psychiatry, LWL University Hospital, Ruhr University Bochum, Bochum, Germany

City

Bochum

Country

Germany

Facility Name

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

City

Dresden

Country

Germany

Facility Name

Department of Psychiatry and Psychotherapy, University of Göttingen, Germany

City

Göttingen

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

31583561

Citation

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.

Results Reference

derived

PubMed Identifier

24345793

Citation

Stamm 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.

Results Reference

derived

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Supraphysiological Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression

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