Raloxifene as an Adjuvant Treatment of the Negative Symptoms of Schizophrenia in Post-menopausal Women

This study is currently recruiting participants.
Verified August 2013 by Fundació Sant Joan de Déu
Sponsor:
Collaborators:
Hospital Sant Joan de Deu
Parc Sanitari Sant Joan de Déu
Stanley Medical Research Institute
Information provided by (Responsible Party):
Fundació Sant Joan de Déu
ClinicalTrials.gov Identifier:
NCT01573637
First received: April 5, 2012
Last updated: August 7, 2013
Last verified: August 2013
  Purpose

The efficacy of raloxifene versus placebo was compared over a six-month period, as an adjuvant treatment of the negative symptoms of schizophrenia in a group of 80 post-menopausal women. The aim of the study is to analyze whether raloxifene has an effect on the positive and negative symptoms of schizophrenia, and on psychopathological symptoms in general, and on social and neuropsychological functioning, and to study the influence of genetic polymorphisms in treatment response.


Condition Intervention Phase
Negative Symptoms of Schizophrenia in Post-menopausal Women.
Drug: Raloxifene
Drug: Lactosa (placebo arm)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Six Month, Double Blind, Placebo-controlled Trial of the Efficacy of Raloxifene as an Adjuvant Treatment of the Negative Symptoms of Schizophrenia in Post-menopausal Women

Resource links provided by NLM:


Further study details as provided by Fundació Sant Joan de Déu:

Primary Outcome Measures:
  • To assess the efficacy of raloxifene (SERM - Selective Estrogen Receptor Modulator) as an adjuvant of antipsychotic treatment in the management of negative symptoms of schizophrenia in post-menopausal women. [ Time Frame: Change in score on the negative subscale of the PANSS from baseline to final assessment at week 24 ] [ Designated as safety issue: Yes ]
    The primary variable of efficacy will correspond to the change in score on the negative subscale of the PANSS from the start of treatment to the final assessment at 24 weeks. Patients will be considered to respond to treatment if the score in the negative subscale is at least 20% lower than at the start of treatment.


Secondary Outcome Measures:
  • To assess the efficacy of raloxifene as an adjuvant of antipsychotic treatment in the management of global symptoms of schizophrenia in postmenopausal women. [ Time Frame: From baseline to week 24 (measurements at Baseline, weeks 4, 12, 24) ] [ Designated as safety issue: No ]
    The results from different scales or test will be measured: at baseline,week 4,12 y 24 for scales (PANSS, SANS, CGI, GAF, CDSS -Calgary, LSP, SIMPSON, UKU, DAS-sv) and at baseline, week 12 and 24 for neuropsychological test (TAVEC, CPT, TMT, STROOP, FAS, WAIS sub-tests).

  • To assess the efficacy of raloxifene as an adjuvant of antipsychotic treatment in the global functioning of postmenopausal women with schizophrenia. [ Time Frame: From baseline to week 24 (measurements at Baseline, weeks 4, 12, 24) ] [ Designated as safety issue: No ]
    The results from different scales or test will be measured: at baseline,week 4,12 y 24 for scales (PANSS, SANS, CGI, GAF, CDSS -Calgary, LSP, SIMPSON, UKU, DAS-sv) and at baseline, week 12 and 24 for neuropsychological test (TAVEC, CPT, TMT, STROOP, FAS, WAIS sub-tests).

  • To assess the efficacy of raloxifene as an adjuvant of antipsychotic treatment in the neuropsychological functioning of post-menopausal women with schizophrenia [ Time Frame: From baseline to week 24 (measurements at Baseline, week 12, week 24) ] [ Designated as safety issue: No ]
    The results from different test will be measured at weeks, baseline, 12 and 24 for neuropsychological test (TAVEC, CPT, TMT, STROOP, FAS, WAIS sub-tests).

  • To control response to treatment as a function of genetic variants in the form of SNP (Single Nucleotide Polymorphisms) that patients present in the alfa (ESR1) and beta (ESR2) estrogenic receptor genes. [ Time Frame: Blood sample collected at Baseline visit ] [ Designated as safety issue: No ]
    Analysis will be done for patients who consented by the Informed Consent Form. The analysis will be carried out by centralized laboratory (Biobanc Institut d´Investigació Sanitària Pere Virgili; Reus, Spain) once all samples will be collected. In the meantime, the samples will be kept frozen at 4oC.

  • To assess the safety of the medication used in this patient population. [ Time Frame: From Baseline to week 24 ] [ Designated as safety issue: Yes ]
    Safety will be assessed during the study by the vigilance of the AEs, SAEs, AR, SARs at each visit. Blood analysis (hemo/chem) will be done at Baseline and at the end (week 24), and clinical scales will be measured at Baseline, week 4,12 y 24 (PANSS, SANS, CGI, GAF, CDSS -Calgary, LSP, SIMPSON, UKU, DAS-sv)


Estimated Enrollment: 80
Study Start Date: July 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Raloxifene hydrochloride 60 mg

Patients fulfilling inclusion criteria and those giving the general informed consent for the study will be randomly allocated to one of the two groups in the trial (placebo or raloxifene) in a 1:1 proportion and in blocks of 4 patients, using the random number tables designed for this purpose.

The dose of raloxifene hydrochloride administered will be 60 mg/day. Both placebo and the raloxifene will be administered over 6 months. Patients will take one single daily dose administered in the morning. Both drugs will be given orally in capsule form. The medication of each of the treatment groups (lactose as placebo, raloxifene) will be introduced into dark green gelatin capsules to guarantee the blinding.

Drug: Raloxifene
The dose of raloxifene hydrochloride administered will be 60 mg/day. Both placebo and the raloxifene will be administered over 6 months. Patients will take one single daily dose administered in the morning. Drug will be given orally in capsule form.
Other Name: Raloxifene hydrochloride 60 mg, Laboratory Esteve.
Placebo Comparator: Lactosa (placebo)

Patients fulfilling inclusion criteria and those giving the general informed consent for the study will be randomly allocated to one of the two groups in the trial (placebo or raloxifene) in a 1:1 proportion and in blocks of 4 patients, using the random number tables designed for this purpose.

The dose of raloxifene hydrochloride administered will be 60 mg/day. Both placebo and the raloxifene will be administered over 6 months. Patients will take one single daily dose administered in the morning. Both drugs will be given orally in capsule form. The medication of each of the treatment groups (lactose as placebo, raloxifene) will be introduced into dark green gelatin capsules to guarantee the blinding.

Drug: Lactosa (placebo arm)
Both placebo and the raloxifene will be administered over 6 months. Patients will take one single daily dose administered in the morning. Drug will be given orally in capsule form.
Other Name: Lactosa

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Diagnosis of schizophrenia according to DSM-IV TR criteria.
  2. Postmenopausal patients. Post-menopausal is defined as 1) aged over 45 years with at least one year of amenorrhea and levels of FSH over 20 UI/L or 2) aged over 50 years with at least one year of amenorrhea.
  3. Patients who have been taking a stable dose of antispsychotic medication for at least the 30 days before the start of the study.
  4. The presence of significant negative symptoms (defined as one or more negative symptoms with a severity of over 4 on the PANSS scale).
  5. General written informed consent by patients or their legal representative.
  6. For the genotypic study, a specific informed consent signed by the patients or legal representative is required.

Exclusion criteria:

  1. A diagnosis of substance abuse/dependence in the previous 6 months.
  2. Mental retardation
  3. A diagnosis of major depression (according to DSM-IV TR criteria).
  4. Endocrine alterations related to sexual hormones, liver insufficiency including cholestasis, severe renal insufficiency.
  5. History or current condition of thromboembolism, breast cancer, abnormal uterine bleeding or stroke.
  6. Patients in hormone replacement therapy.
  7. Known allergy or hypersensitivity to the active ingredient of the investigational drug, or to any of its excipients or lactose.
  8. To be receiving treatment in another clinical trial.
  9. To present any severe concomitant disease that in the researcher's opinion can compromise completion of the study or affect the patient's tolerance to this treatment.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01573637

Contacts
Contact: Judith Usall, MD PhD +34 93 640 63 50 ext 2347 jusall@pssjd.org

Locations
Spain
Corporació Sanitària Parc Taulí Recruiting
Sabadell, Barcelona, Spain, 08208
Contact: Gemma Garcia-Parés, MD PdD    +34 610 23 07 13    GGarcia@tauli.cat   
Contact: Jesús Vicente Cobo, Psychiatrist    +34 610 23 07 20    JCobo@tauli.cat   
Principal Investigator: Gemma Garcia-Parés, Psychiatrist         
Sub-Investigator: Jesús Vicente Cobo, Psychiatrist         
Sub-Investigator: Lourdes Nieto, Psichologist         
Parc Sanitari Sant Joan de Déu Recruiting
Sant Boi de Llobregat, Barcelona, Spain, 08830
Contact: Judith Usall, MD PhD    +34 93 640 63 50 ext 2347    jusall@pssjd.org   
Contact: María Elena Huerta, Psychologist    +34 93 640 63 50 ext 2347    mehuerta@pssjd.org   
Principal Investigator: Judith Usall, PhD         
Sub-Investigator: María Elena Huerta, Psychologist         
Sub-Investigator: Marta Coromina, Psychologist         
Sub-Investigator: Belén Arranz, Psychiatrist         
Sub-Investigator: Mercedes Roca, Psychiatrist         
Sub-Investigator: Susana Ochoa, Psychologist         
Hospital Psiquiàtric Institut Pere Mata Recruiting
Reus, Tarragona, Spain, 43206
Contact: Javier Labad, Dr    +34 977 333 85 65 ext 395    labadj@gmail.com   
Contact: Marta Creus, Psychologist    +34 977 333 85 65 ext 395    creusm@peremata.com   
Principal Investigator: Javier Labad, Psychiatrist         
Sub-Investigator: Marta Creus, Psychologist         
Sub-Investigator: José Franco, Psychiatrist         
Sub-Investigator: Julio César Reyes, Psychiatrist         
Sub-Investigator: Lourdes Martorell, Geneticist         
Sponsors and Collaborators
Fundació Sant Joan de Déu
Hospital Sant Joan de Deu
Parc Sanitari Sant Joan de Déu
Stanley Medical Research Institute
Investigators
Principal Investigator: Judith Usall, PhMD Parc Sanitari Sant Joan de Déu
Principal Investigator: Javier Labad Arias, PhMD Hospital Psiquiàtric Institut Pere Mata de Reus
Principal Investigator: Gemma García-Parés, PhMD Corporació Sanitária Parc Taulí
  More Information

Additional Information:
Publications:
Kulkarni J, Gurbich C, Lee SJ, et al. Piloting the effective therapeutic dose of adjunctive selective estrogen receptor modulator treatment in postmenopausal women with schizophrenia. Psychoneuroendocrinology 2010; 35(8):1142-7.
Zavratnik A, Zegura B, Marc J, Prezelj J, Pfeifer M. XbaI polymorphism of the estrogen receptor alpha gene influences the effect of raloxifene on the endothelial function. Maturitas 2010; 67:84-90.

Responsible Party: Fundació Sant Joan de Déu
ClinicalTrials.gov Identifier: NCT01573637     History of Changes
Other Study ID Numbers: FSJD-RAL-2010
Study First Received: April 5, 2012
Last Updated: August 7, 2013
Health Authority: Spain: Spanish Agency of Medicines
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Fundació Sant Joan de Déu:
schizophrenia in post-menopausal women
schizophrenia
negative schizophrenia
schizophrenia in women
ralixifene
raloxifen
raloxifeno
negative symptoms of schizophrenia
negative symptoms in schizophrenia
schizophrenia symptoms
negative symptoms of psychosis

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Raloxifene
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Estrogen Antagonists

ClinicalTrials.gov processed this record on April 17, 2014