Anti-Estrogens - A Potential Treatment for Bipolar Affective Disorder in Women?

NCT00206544 | Completed Phase 2

• 3 other identifiers: APRC 77/0203T-415284319
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

OBJECTIVE: To test the use of two adjunctive hormonal agents in a 28 day three-arm, double-blind, placebo-controlled study in the treatment of acute mania/hypomania. HYPOTHESIS: That women receiving adjunctive Tamoxifen or Progesterone will demonstrate a more rapid and more substantial decrease in manic symptoms over the course of the study than women receiving adjunctive placebo. STUDY POPULATION: Sixty females with a current diagnosis of Bipolar Affective Disorder or Schizoaffective disorder - Manic Phase, according to the operationalised criteria of the Diagnostic and Statistical Manual, 4th edition (DSM-IV) of the American Psychiatric Association. STUDY MEDICATION: Tamoxifen. One third of patients (twenty) will be randomized to receive adjunctive Tamoxifen at 40 mg/day for 28 days. The Tamoxifen will be administered within a plain capsule to maintain "blinding" of treatment arm. Progesterone. One third of patients (twenty) will be randomized to receive adjunctive oral Provera (progesterone) at 20 mg/day. The Progesterone will be administered within a plain capsule identical to that used with Tamoxifen. Placebo. The remaining one third of patients will be randomized to receive adjunctive placebo (inert substance). The placebo substance will be administered within a plain capsule identical to that used with Tamoxifen and Progesterone. STUDY EVALUATIONS: Data will be collected over a 28-day period for each patient. Visits will be performed at baseline, and then at weekly intervals. A total of five visits will be completed for each patient. The following evaluations will be performed:

• Psychiatric evaluation to determine diagnosis. (Baseline visit only)
• General clinical evaluation including medical history, current conditions and a non-invasive physical examination, body weight, vital signs. (Baseline visit only)
• Medication history (baseline and evaluation visits).
• Demographics (baseline visits only).
• Completion of clinical rating scales; CARS-M, PANSS, MADRS, AIMS, Barnes Akathisia scale (BA), and Simpson-Angus scale (SA) (baseline and evaluation visits). A Menstrual Cycle Interview and a cognitive assessment (RBANS) will be performed at baseline and endpoint (day 28) visit.
• Laboratory tests including; Serum levels of mood stabilizer, luteinizing hormone (LH), follicle-stimulating hormone (FSH), Estrogen, Progesterone, Prolactin, dehydroepiandrosterone (DHEA), Testosterone and protein kinase C(PKC) (baseline and evaluation visits).
• Inclusion/exclusion checklist (baseline visit only).
• Informed consent (baseline visit only).

Conditions

Bipolar Disorder; Mania; Schizoaffective Disorder

Keywords

Bipolar Affective Disorder; Mania; Anti-Estrogen; Schizoaffective Disorder; Mood

Outcome Measures

Primary Outcomes (1)

• Scores on CARS-M Scale at trial completion

  Baseline and weeks 1, 2, 3 and 4

Secondary Outcomes (5)

• Scores on PANSS at trial completion (4 weeks)

  Baseline and weeks 1, 2, 3 and 4

• Scores on MADRS at trial completion (4 weeks)

  Baseline and weeks 1, 2, 3 and 4

• Scores on Adverse Symptom Checklist at trial completion (4 weeks)

  Baseline and weeks 1, 2, 3 and 4

• Change in hormone levels over trial duration

  Baseline and weeks 1, 2, 3 and 4

• Scores on RBANS at trial completion (4 weeks)

  Baseline and week 4

Study Arms (3)

1

ACTIVE COMPARATOR

Tamoxifen 40 mg daily

Drug: Tamoxifen

2

ACTIVE COMPARATOR

Progesterone 20 mg daily

Drug: Progesterone

3

PLACEBO COMPARATOR

Placebo daily

Other: placebo

Interventions

Tamoxifen DRUG

40 mg daily of adjunctive tamoxifen in oral capsule

1

Progesterone DRUG

20 mg daily of adjunctive progesterone in oral capsule

2

placebo OTHER

adjunctive placebo daily in oral capsule

3

Eligibility Criteria

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

You may qualify if:

• Female patients who have a current diagnosis of Bipolar Affective Disorder (Manic phase) or Schizoaffective Disorder (Bipolar type in manic phase).
• Female patients who are able to give informed consent.

You may not qualify if:

• Female patients who are pregnant or lactating.
• Female patients with postpartum psychosis or related disorder.
• Female patients with known abnormalities in the hypothalamo-pituitary gonadal-axis, thyroid dysfunction, central nervous system tumors.
• Female patients taking estrogen preparations such as the oral contraceptive pill.
• Female patients currently taking interacting drugs including warfarin, aminoglutethimide, diuretics, methyldopa, theophylline, fluoxetine, calcium channel blockers and non-steroidal anti-inflammatory drugs.
• Female patients whose psychotic illness is directly due to illicit drugs or who have a history of substance abuse or dependence during the last 6 months.
• Females with any significant unstable medical illness such as cardiovascular disease, renal disease, Addisons disease, thromboembolic disorders, epilepsy, diabetes etc.

Sponsors & Collaborators

• The Alfred: lead
• Stanley Medical Research Institute: collaborator
• National Health and Medical Research Council, Australia: collaborator

Study Sites (1)

Bayside Health - The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Related Links

• Alfred Psychiatry Research Centre

MeSH Terms

Conditions

Bipolar Disorder; Mania; Psychotic Disorders

Interventions

Tamoxifen; Progesterone

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Officials

• Jayashri Kulkarni, MBBS, MPM, FRANZCP, PhD

  Bayside Health / Monash University

  PRINCIPAL INVESTIGATOR

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

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 21, 2005
• Study Start: January 1, 2004
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: October 24, 2008

Record last verified: 2008-10

Locations

AU (1)