Biochemical Brain Changes Correlated With The Antidepressant Effect Of Thyroid Hormones

This study has been completed.
Sponsor:
Collaborator:
National Alliance for Research on Schizophrenia and Depression
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00562367
First received: November 20, 2007
Last updated: November 21, 2007
Last verified: November 2007
  Purpose

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:

  1. All depressed subjects, when compared with normal controls, will present lower baseline levels of compounds characteristic for the high-energy phosphate metabolism.
  2. 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.

Condition Intervention
Major Depressive Disorder
Drug: Cytomel (liothyronine)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Biochemical Brain Changes Correlated With The Antidepressant Effect Of Thyroid Hormones

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • change in depression (as measured by Ham-D-17) over the 4 weeks study [ Time Frame: 4 weeks ]

Secondary Outcome Measures:
  • change in bioenergetic metabolism (e.g., NTP and PCr) as measured by phosphorus magnetic resonance spectroscopy (P31-MRS) [ Time Frame: 4 weeks ]

Enrollment: 30
Study Start Date: October 2001
Study Completion Date: September 2004
Intervention Details:
    Drug: Cytomel (liothyronine)
    Cytomel (liothyronine) 25-50 mcg/day for 4 weeks
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00562367

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Alliance for Research on Schizophrenia and Depression
Investigators
Principal Investigator: Dan V Iosifescu, MD Massachusetts General Hospital
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00562367     History of Changes
Other Study ID Numbers: 2001-P-000836
Study First Received: November 20, 2007
Last Updated: November 21, 2007
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Antidepressive Agents
Hormones
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014