Clinical trial NCT00208897: Does Fluoxetine Have an Effect on the CNS CRF Systems in Women Abused in Childhood?
Official title: Does Fluoxetine Reverse the Effects of Early Life Stress on the CNS Corticotropin-Releasing Factor System and Improve Psychological and Neuroendocrine Function?: A Therapy Outcome Study in Women With Childhood Abuse Experiences
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depressive Disorder
Keywords: Early Life Stress
HPA-axis
CRF
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2005-09-21
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this project is to determine whether treatment with the SSRI, fluoxetine versus placebo reverses alterations in the central CRF system induced by early life stress experiences (i.e. childhood sexual and/or physical abuse) in cases with and without major depression. We also evaluate whether neuroendocrine changes after SSRI treatment correlate with clinical improvement.

Detailed description: We compare indices of central CRF activity (i.e. ACTH and cortisol response to CRF stimulation test) before and after 8 weeks of treatment with either fluoxetine or placebo between women with a history of childhood abuse (early life stress, ELS) and current major depression (ELS/MDD), women with a history of childhood abuse without major depression (ELS/non-MDD), and women without a history of childhood abuse and major depression (non-ELS/MDD). Changes in neuroendocrine responses to CRF are correlated with psychological outcome measures. We hypothesize that treatment with fluoxetine will normalize altered neuroendocrine responsiveness in cases with ELS and that this normalization will be correlated with improvement of symptoms of depression and anxiety.

Eligibility criteria: Inclusion Criteria:

1. For all subjects female gender;
2. For subjects assigned to the MDD groups, current DSM-IV diagnosis of MDD;
3. For subjects assigned to the early-life stress group, repeated (once per month or more for at least year) sexual or physical abuse before the age of 12 years by a perpetrator at least 5 years older at the time;
4. For all subjects, age of 18 to 45 years;
5. Regular menstrual cycle and assessment in the early follicular phase as verified by sex steroid measures.

Exclusion Criteria:

1. For all subjects, gender identity disorders;
2. For all subjects assigned to non-MDD groups, DSM-IV diagnosis of current MDD;
3. For all subjects assigned to the group without early-life stress, major stress experiences before the age of 12 years, such as separation from parents, neglect, parental loss, accidents, severe illness or natural disaster;
4. For all subjects, significant medical illness, such as gastrointestinal, neurological, endocrine, cardiovascular, pulmonary, renal, hepatic, immunological or hematological disease, organic brain disease, or cancer as determined by history, physical examination, ECG, and laboratory tests;
5. Pregnancy or nursing;
6. For all subjects, past or current presence of psychotic symptoms or bipolar disorder;
7. For all subjects, current presence of psychoactive substance abuse/dependency or eating disorders;
8. For all subjects, hormonal medication;
9. For all subjects, psychotropic medication in the four weeks prior to study entry;
10. For all subjects, inability to provide informed consent.

Primary outcomes:
measure: Plasma ACTH and cortisol concentrations before and after administration of 1 microgram per kg ovine CRF
timeFrame: 6 hours
Secondary outcomes:
measure: Symptom Rating Scales for Depression, Anxiety and PTSD as well as general well-being
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Department of Psychiatry and Behavioral Sciences
state: Georgia
Study officials:
affiliation: Emory University-Dept. of Psychiatry and Behavioral Sciences
name: Christine M Heim, PhD
role: PRINCIPAL_INVESTIGATOR
References: