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Biochemical Brain Changes Correlated With The Antidepressant Effect Of Thyroid Hormones

Primary Purpose

Major Depressive Disorder

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Cytomel (liothyronine)
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional basic science trial for Major Depressive Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • DSM-IV diagnostic criteria for MDD (diagnosed with the use of SCID)
  • Written informed consent
  • Men or women aged 18-65
  • A baseline Hamilton-D17 score of > 16.

Exclusion Criteria:

  • Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment.
  • Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy)
  • Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
  • History of seizure disorder,
  • History or current diagnosis of the following DSM-IV psychiatric illness: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, patients with mood congruent or mood incongruent psychotic features, patients with substance dependence disorders, including alcohol, active within the last 12 months.
  • History or current diagnosis of dementia, or a score of < 26 on the Mini Mental Status Examination (Folstein, 1975) at the screening visit.
  • History of multiple adverse drug reactions or allergy to the study drugs.
  • Patients with mood congruent or mood incongruent psychotic features.
  • Patients having shown minimal or no response to a standard course of antidepressant treatment with an SSRI. A standard course will be defined as the following medications taken for > 4 weeks: fluoxetine > 20 mg/day, sertraline > 50 mg/day, paroxetine > 20 mg/day, fluvoxamine > 50 mg/day, citalopram > 20 mg/day, venlafaxine > 150 mg/day.
  • Clinical or laboratory evidence of hypothyroidism.
  • Patients who have had electroconvulsive therapy (ECT) within the 6 months preceding baseline.
  • History of intolerance to Cytomel
  • History of cardiac pathology or diabetes

Sites / Locations

  • Massachusetts General Hospital

Outcomes

Primary Outcome Measures

change in depression (as measured by Ham-D-17) over the 4 weeks study

Secondary Outcome Measures

change in bioenergetic metabolism (e.g., NTP and PCr) as measured by phosphorus magnetic resonance spectroscopy (P31-MRS)

Full Information

First Posted
November 20, 2007
Last Updated
November 21, 2007
Sponsor
Massachusetts General Hospital
Collaborators
National Alliance for Research on Schizophrenia and Depression
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1. Study Identification

Unique Protocol Identification Number
NCT00562367
Brief Title
Biochemical Brain Changes Correlated With The Antidepressant Effect Of Thyroid Hormones
Official Title
Biochemical Brain Changes Correlated With The Antidepressant Effect Of Thyroid Hormones
Study Type
Interventional

2. Study Status

Record Verification Date
November 2007
Overall Recruitment Status
Completed
Study Start Date
October 2001 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
September 2004 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Alliance for Research on Schizophrenia and Depression

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
We propose to investigate structural and biochemical brain abnormalities in depressed subjects, and the relationship between the presence of such abnormalities and treatment outcome. We will recruit N=20 subjects with major depression disorder and N=20 matched normal controls. The depressed subjects would have previously not responded to an adequate trial with a selective serotonin reuptake inhibitor (SSRI). These depressed subjects will be treated for 4 weeks with the same SSRI antidepressant and with adjuvant triiodothyronine (T3). Structural magnetic resonance images (MRI) and then Phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI) data will be obtained two times for each patient (at the beginning and at the end of the study) and one time for the normal controls. We will measure for each depressed subject the number of white matter hyperintensities (WMH); we will also measure the degree of change from baseline in several compounds characteristic for the cellular high-energy phosphate metabolism: the phosphocreatine/inorganic phosphate ratio and the beta-nucleoside triphosphate. We will compare the severity of WMH and the high-energy phosphate metabolism in two groups of depressed subjects (those responding and those not responding to thyroid hormone augmentation) and the normal controls. We hypothesize that: All depressed subjects, when compared with normal controls, will present lower baseline levels of compounds characteristic for the high-energy phosphate metabolism. Depressed subjects responding to T3 augmentation, when compared with subjects not responding to T3 augmentation, will present a larger increase of the high-energy phosphate metabolism.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Cytomel (liothyronine)
Intervention Description
Cytomel (liothyronine) 25-50 mcg/day for 4 weeks
Primary Outcome Measure Information:
Title
change in depression (as measured by Ham-D-17) over the 4 weeks study
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
change in bioenergetic metabolism (e.g., NTP and PCr) as measured by phosphorus magnetic resonance spectroscopy (P31-MRS)
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: DSM-IV diagnostic criteria for MDD (diagnosed with the use of SCID) Written informed consent Men or women aged 18-65 A baseline Hamilton-D17 score of > 16. Exclusion Criteria: Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment. Pregnant women or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy) Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease History of seizure disorder, History or current diagnosis of the following DSM-IV psychiatric illness: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, patients with mood congruent or mood incongruent psychotic features, patients with substance dependence disorders, including alcohol, active within the last 12 months. History or current diagnosis of dementia, or a score of < 26 on the Mini Mental Status Examination (Folstein, 1975) at the screening visit. History of multiple adverse drug reactions or allergy to the study drugs. Patients with mood congruent or mood incongruent psychotic features. Patients having shown minimal or no response to a standard course of antidepressant treatment with an SSRI. A standard course will be defined as the following medications taken for > 4 weeks: fluoxetine > 20 mg/day, sertraline > 50 mg/day, paroxetine > 20 mg/day, fluvoxamine > 50 mg/day, citalopram > 20 mg/day, venlafaxine > 150 mg/day. Clinical or laboratory evidence of hypothyroidism. Patients who have had electroconvulsive therapy (ECT) within the 6 months preceding baseline. History of intolerance to Cytomel History of cardiac pathology or diabetes
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dan V Iosifescu, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16086620
Citation
Iosifescu DV, Nierenberg AA, Mischoulon D, Perlis RH, Papakostas GI, Ryan JL, Alpert JE, Fava M. An open study of triiodothyronine augmentation of selective serotonin reuptake inhibitors in treatment-resistant major depressive disorder. J Clin Psychiatry. 2005 Aug;66(8):1038-42. doi: 10.4088/jcp.v66n0812.
Results Reference
result
PubMed Identifier
18206856
Citation
Iosifescu DV, Bolo NR, Nierenberg AA, Jensen JE, Fava M, Renshaw PF. Brain bioenergetics and response to triiodothyronine augmentation in major depressive disorder. Biol Psychiatry. 2008 Jun 15;63(12):1127-34. doi: 10.1016/j.biopsych.2007.11.020. Epub 2008 Jan 22.
Results Reference
derived

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Biochemical Brain Changes Correlated With The Antidepressant Effect Of Thyroid Hormones

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