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Trial record 4 of 67 for:    Behaviors and Mental Disorders[CONDITION-BROWSE-BRANCH] | Recruiting, Not yet recruiting, Available Studies | ( Map: Illinois, United States ) | NIH, U.S. Fed

Identifying Neural Mechanisms of PTSD Symptom Reduction Induced by Estrogen

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ClinicalTrials.gov Identifier: NCT03371654
Recruitment Status : Recruiting
First Posted : December 13, 2017
Last Update Posted : December 13, 2017
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Mohammed Milad, University of Illinois at Chicago

Brief Summary:
This study aims to first identify the optimal estradiol (E2) dose that best engages the fear extinction network among healthy women using oral contraceptives. The second objective is to then evaluate the impact of this optimal E2 dose, when administered in conjunction with 5 sessions of Prolonged Exposure therapy, on the functional activity of the fear extinction network of women with clinically significant posttraumatic stress disorder symptoms. This approach will elucidate the neural mechanisms underlying effective exposure treatment for these symptoms, and will document how estradiol could be used as adjunct to enhance the outcome of extinction-based therapies.

Condition or disease Intervention/treatment Phase
Stress Disorders, Post-Traumatic Healthy Drug: Estradiol Drug: Placebo Phase 4

Detailed Description:
Prolonged-exposure (PE) therapy is the treatment of choice for posttraumatic stress disorder (PTSD). Despite its efficacy, a significant number of individuals will not benefit from it or might drop out before the completion of all sessions. This underlies the importance of finding ways to enhance the efficacy of PE in order to improve the life quality of individuals suffering from PTSD. It is now widely accepted that extinction learning paradigms used in fundamental studies are useful laboratory analogs to PE. Studies in healthy controls have suggested that elevated estrogen levels benefit extinction learning by promoting its consolidation and thus enhancing its recall when tested later for it. This is also being reflected by changes in the activation of brain regions forming the fear extinction network, including the amygdala, dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortex (vmPFC). It is still unknown whether estradiol (E2) administration can modulate the activation of the fear extinction network in oral contraceptive (OC) users and which E2 dose could yield the best results. The R61 phase of the current study will aim to establish which of two E2 doses (placebo (Plc), 2mg or 4mg) can best engage the fear extinction network in healthy women using OC by exposing participants to a validated fear conditioning and extinction protocol. Functional fMRI (BOLD signal) and psychophysiological measures (skin conductance responses - SCR) will be used to test the following hypotheses: 1) E2 administration will enhance extinction recall (indexed by lower SCR) in a dose-response manner; 2) E2 administration will increase vmPFC and decrease dACC and amygdala activations during recall in a dose-response manner. Once the optimal E2 dose has been identified, the R33 phase will examine the impact of E2 administration (relative to Plc) in conjunction with 5 PE sessions in OC users women having significant symptoms of PTSD. Participants will be exposed to the fear conditioning and extinction protocol before and after PE. BOLD signal, SCR as well as symptom severity will be used before and after treatment to test these hypotheses: 1) During extinction recall, both groups will show lower SCR at post- relative to pre-PE, with E2+PE group showing the strongest effect. 2) Extinction-induced activations will be higher in the vmPFC and lower in the dACC and amygdala in post relative to pre-PE, with E2+PE group showing the strongest effect. 3) Information flow between the extinction nodes will improve following therapy (indexed by dynamic-causal modeling), with stronger effects in the E2+PE group. 4) PTSD symptom severity will be lower in the E2+PE group relative to the Plc+PE group following treatment, as well as at the 3 and 6-month follow-up assessments. 5) PTSD symptom reduction will correlate with BOLD and SCR changes observed during extinction recall. These findings will elucidate the neural mechanisms underlying effective exposure treatment for fear-based symptoms, and will reveal how E2 could be an adjunct to enhance the efficacy of extinction-based therapies such as PE.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 79 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Identifying Neural Mechanisms of PTSD Symptom Reduction Induced by Combined Estrogen and Prolonged Exposure Therapy
Actual Study Start Date : November 29, 2017
Estimated Primary Completion Date : July 31, 2019
Estimated Study Completion Date : July 31, 2019


Arm Intervention/treatment
Experimental: Estradiol 2mg
Women will be randomized and asked to take the study drug (2mg E2 dose) at home 5 hours before their appointment on Day 2.
Drug: Estradiol
Synthetic estradiol (2mg or 4mg) will be administered

Experimental: Estradiol 4mg
Women will be randomized and asked to take the study drug (4mg E2 dose) at home 5 hours before their appointment on Day 2.
Drug: Estradiol
Synthetic estradiol (2mg or 4mg) will be administered

Placebo Comparator: Placebo
Women will be randomized and asked to take the study drug (Placebo) at home 5 hours before their appointment on Day 2.
Drug: Placebo
Placebo will be administered




Primary Outcome Measures :
  1. The investigators will use skin conductance responses (SCR) during fear conditioning, extinction learning, and extinction recall to measure differential fear acquisition and extinction. [ Time Frame: 2 years ]
    The investigators expect a dose-response effect during recall, with the 4mg dose inducing the best recall (lowest SCR), the 2mg yielding moderate recall, and the Placebo inducing the worst recall (highest SCR).



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. 18 - 45 years of age
  2. Right-handed (Edinburgh Inventory - Oldfield 1971)
  3. SCID diagnosis consistent with no current or past history of Axis I psychiatric disorders
  4. To be matched for age, and years of education, as well as self-identified race/ethnicity.
  5. Use of oral contraceptives (20mcg ethinyl estradiol, 2nd or 3rd generation, monophasic)

Exclusion Criteria:

  1. Psychiatric, neurologic or medical condition that would interfere with study procedures or confound results, ascertained by history.
  2. History of seizure or significant head trauma (i.e., extended loss of consciousness, neurological sequelae, or known structural brain lesion)
  3. History of Axis I psychiatric diagnosis; e.g., history of substance use disorder, psychotic disorder, bipolar disorder, tic disorder, or eating disorder.
  4. Use of psychotropic medication within 4 weeks prior to study (within 6 weeks for fluoxetine, or other long-lived compounds; within one year for neuroleptics).
  5. Pregnancy (to be ruled out by urine ß-HCG).
  6. Metallic implants or devices contraindicating magnetic resonance imaging.
  7. History of a hormone-responsive cancer.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03371654


Contacts
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Contact: Alyssa Frederick, MA 888-686-5591 emotion@uic.edu
Contact: Kayla Kreutzer, BA 888-686-5591 ordstudy@uic.edu

Locations
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United States, Illinois
University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60608
Contact: Alyssa Frederick, MA    888-686-5591    emotion@uic.edu   
Principal Investigator: Mohammed Milad, PhD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Lily Brown, PhD    215-746-3327    lilybr@pennmedicine.upenn.edu   
Principal Investigator: Edna Foa, PhD         
Sponsors and Collaborators
University of Illinois at Chicago
National Institute of Mental Health (NIMH)

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Responsible Party: Mohammed Milad, Professor, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT03371654     History of Changes
Other Study ID Numbers: 2017-0689
R61MH111907 ( U.S. NIH Grant/Contract )
First Posted: December 13, 2017    Key Record Dates
Last Update Posted: December 13, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Estradiol
Polyestradiol phosphate
Estrogens
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female