A Definitive Estrogen Patch Study (ADEPT)

NCT00357006 | Completed Phase 2 Results DMC

• 2 other identifiers: 202/0405T-742
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

OBJECTIVE: To test the use of adjunctive estrogen in a 8 week, three-arm, double-blind, placebo-controlled study in the treatment of psychotic symptoms in women with schizophrenia. HYPOTHESIS: That women receiving adjunctive estrogen will demonstrate significantly greater improvements in the symptoms of schizophrenia than women receiving adjunctive placebo. STUDY POPULATION: 180 women will be recruited over a three-year period across three sites. Participant will be of potential child-bearing age (Pre-menopausal and Post-menarche) with a current diagnosis of Schizophrenia, Schizophreniform Disorder, or Schizoaffective Disorder (not in manic phase)according to the Mini International Neuropsychiatric Interview (MINI). STUDY MEDICATION: Estradiol. One third of the participants (n=60) will be randomised to receive adjunctive 100mcg Estradiol; one third of the participants (n=60) will be randomised to receive adjunctive 200mcg Estradiol n=60; and, one third of the participants (n=60) will be randomised to receive adjunctive placebo n=60). All patches will be covered with identical adhesive contact to ensure the "blind" is maintained. STUDY EVALUATIONS: Data will be collected over a two-month period for each participant. Visits will be performed at baseline, and then at weekly or fortnightly intervals. A total of six visits will be completed for each participant. The following evaluations will be performed: i) Inclusion/exclusion checklist. (Baseline visit only) ii) Informed consent. (Baseline visit only) iii)psychiatric evaluation to determine diagnosis. (Baseline visit only) iv) General clinical evaluation including medical history, current conditions and a non-invasive physical examination, body weight, vital signs. (Baseline and endpoint visits) v) Medication history. (Baseline and evaluation visits) vi) Demographics. (Baseline visits only) vii) The primary outcome measures will be the Positive and Negative Syndrome Scale (PANSS), which will be taken at weeks 1, 2, 4 and 8 of the trial. Cognitive testing will take place at baseline and 8 weeks. Side effects will be assessed at weeks 1, 2, 4, 6, and 8 to measure changes in subject's reported side effects during the trial. viii) Laboratory tests including; Serum levels of mood stabiliser, LH, FSH, Estrogen, Progesterone, Prolactin, DHEA,Testosterone and(Baseline and evaluation visits).

Conditions

Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder(Not in Manic Phase)

Keywords

Schizophrenia; Estrogen; Psychosis

Outcome Measures

Primary Outcomes (1)

• Positive and Negative Syndrome Scale (PANSS)

  The Positive and Negative Syndrome Scale (PANSS) is a well validated, standardized method of evaluating and monitoring psychotic symptoms. The PANSS assesses: positive (hallucinations, delusions, thought disorder), negative (blunted affect, abstract thinking and general symptomatology. The positive and negative subscale each consist of 7 items rated from 1(absent) - 7(extreme) with a minimum score = 7, maximum score = 49. The general subscale consists of 16 items with a minimum score = 16, maximum score = 112. A Total PANSS score (positive+ negative + general scores) has a minimum of 30 and maximum of 210. Higher scores represent more severity in symptoms.

  Baseline and week 8

Secondary Outcomes (4)

• Cognitive Performance (RBANS Scores)

  baseline and week 8

• Scores on MADRS at Trial Completion

  Baseline and week 8

• Scores on Adverse Symptom Checklist at Trial Completion

  Baseline and weeks 1, 2, 4, 6, 8

• Change in Hormone Levels Over Trial Duration

  Baseline and weeks 1, 4 and 8.

Study Arms (3)

1

ACTIVE COMPARATOR

100 mcg Estradiol

Drug: Estradiol

2

ACTIVE COMPARATOR

200 mcg Estradiol

Drug: Estradiol

3

PLACEBO COMPARATOR

adjunctive transdermal placebo

Other: placebo

Interventions

Estradiol DRUG

100 mcg adjunctive transdermal estradiol

1

placebo OTHER

adjunctive transdermal placebo

3

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female participants of potential child-bearing age (Pre-menopausal and Post-menarche)
• Female participants who meet the MINI (Mini International Neuropsychiatric Interview for DSM-IV) diagnostic criteria for current psychotic disorder or have a current DSM-IV diagnosis of Schizophrenia, Schizophreniform Disorder, or Schizoaffective Disorder (not in manic phase).
• Female participants with a PANSS positive score greater than 15 and/or a PANSS negative score greater than 15.
• Female participants who are able to give informed consent
• Female participants receiving 2-20mg daily Risperidone equivalents for at least 4 weeks.

You may not qualify if:

• Female participants who are pregnant or lactating.
• Female participants with known severe abnormalities in the hypothalamo-pituitary gonadal axis, thyroid dysfunction, central nervous system tumours, history of thromboembolic disorders, severe renal failure, severe hepatic failure, cardiac disease, epilepsy or other serious medical conditions which would contraindicate estrogen use.
• Female participants already taking oral estrogen preparations containing greater then 30mcg estradiol.
• Post-menopausal or pre-menarche female participants.
• Female participants whose psychotic illness meets DSM-IV criteria for substance-induced psychotic disorder.
• Female participants who have a current diagnosis of Schizoaffective Disorder and are in a manic phase.

Sponsors & Collaborators

• The Alfred: lead
• Stanley Medical Research Institute: collaborator

Study Sites (1)

Bayside Health - The Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

Related Publications (1)

• Thomas N, Gurvich C, Hudaib AR, Gavrilidis E, de Castella RA, Thomas EH, Kulkarni J. Serum estradiol as a blood-based biomarker predicting hormonal treatment outcomes in women with schizophrenia. Psychoneuroendocrinology. 2021 Apr;126:105165. doi: 10.1016/j.psyneuen.2021.105165. Epub 2021 Feb 10.

  PMID: 33609856 DERIVED

Related Links

• Monash Alfred Psychiatry Research Centre

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Prof Jayashri Kulkarni
• Organization: Monash Alfred Psychiatry Research Centre

j.kulkarni@alfred.org.au

+61 390766924

Study Officials

• Jayashri Kulkarni, MBBS, MPM, FRANZCP, PhD

  Bayside Health / Monash University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: July 26, 2006
• First Posted: July 27, 2006
• Study Start: July 1, 2006
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2013
• Last Updated: May 12, 2015
• Results First Posted: April 1, 2015

Record last verified: 2015-05

Locations

AU (1)