Fluoxetine Prevention Trial

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2012 by University of California, Los Angeles
Sponsor:
Collaborator:
Beckman Research Institute
Information provided by (Responsible Party):
Daniel H. Silverman, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01615055
First received: June 6, 2012
Last updated: June 7, 2012
Last verified: June 2012
  Purpose

Many cancer survivors are experiencing problems with memory and other cognitive abilities following cancer treatment. Little is known concerning the contributions of potentially preventive therapies on cognitive function, but animal studies have pointed to the potential value of the medication fluoxetine in this context. We aim to determine whether six months of fluoxetine therapy can preserve brain function in patients who have undergone chemotherapy, and examine potential biological mechanisms for its protective effects in humans. If use of fluoxetine in cancer patients can be validated in this manner, it will represent the first drug demonstrated to prevent cerebral dysfunction associated with exposure to chemotherapy. Moreover, as this involves an agent that is already FDA-cleared for other indications, widely commercially available throughout the U.S. and other parts of the world, and relatively inexpensive since it is obtainable in generic formulations, it would represent a pharmacologic approach that is amenable to rapid translation to the clinical setting.


Condition Intervention
Cognitive Dysfunction
Drug: Fluoxetine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Prevention of Cognitive Decline After Chemotherapy, With Fluoxetine Treatment

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Change from baseline in regional cerebral metabolism [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Durability of the protective effect of fluoxetine [ Time Frame: 6 months and 1 year ] [ Designated as safety issue: Yes ]
  • Change from baseline in neuropsychological (cognitive, functional) test results [ Time Frame: Baseline, 6 months, and 1 year ] [ Designated as safety issue: Yes ]
  • Correlation between cognitive functioning and cerebral metabolism by correlating neuropsychological testing results with PET imaging [ Time Frame: Baseline, 6 months, and 1 year ] [ Designated as safety issue: Yes ]
  • Correlation between inflammatory cytokines and cerebral metabolism by correlating blood cytokine marker levels with PET imaging [ Time Frame: Baseline, 6 months, and 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 376
Study Start Date: October 2012
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fluoxetine tablets Drug: Fluoxetine
20-40 mg fluoxetine po qd for 6 months
Other Name: Prozac
Placebo Comparator: Placebo tablets Drug: Placebo
same as above with pharmacologically inactive tablets
Other Name: "sugar" pill

Detailed Description:

Systematic studies of adverse cognitive and neurobiological changes subsequent to chemotherapy for lymphoma, breast, and other cancers have attracted substantial interest in the past decade. Little is known, however, concerning the feasibility and effects of potentially protective therapies on cerebral function in patients undergoing chemotherapy. Animal models have recently proved useful in examining some of the toxic effects of chemotherapy agents on working memory and other abilities, as well as on biological properties such as proliferation and survival of neuronal precursors involved in hippocampal neurogenesis. Such models have also proved useful for testing potential neuroprotective properties of agents given before, during and/or after chemotherapy. For example, impairment in spatial working memory and decreased hippocampal neurogenesis is induced in rats by the chemotherapy agent methotrexate, but co-administration of the (FDA-cleared and commercially available) drug fluoxetine has been shown to counteract the negative long-term effects on memory and hippocampal neurogenesis otherwise occurring after methotrexate administration. To determine whether such a strategy could be effective in counteracting effects that chemotherapy may have on cerebral function in humans, well-controlled experimental data obtained with cancer patients is needed.

This investigation will employ a prospective, randomized, double-blinded, placebo-controlled design, to provide a rigorous test of whether fluoxetine, a drug with a long-standing excellent safety profile in humans most commonly marketed as an antidepressant, can offer protection to breast cancer or lymphoma patients against changes in cerebral function occurring after chemotherapy (Specific Aim 1). It will further provide a test of the durability of any protective effects beyond the period during which fluoxetine is used, by re-assessing function approximately 6 months after completion of the regimen (Specific Aim 2). Cerebral function will be assessed by determining distributions of regional cerebral metabolism, previously demonstrated to sensitively detect functional alterations and closely reflect diminished cognitive abilities with high statistical power, using positron emission tomography with the glucose analog radiotracer [F-18]fluorodeoxyglucose. Neuropsychologic testing will be conducted in parallel with neuroimaging studies and, as a step towards understanding mechanisms underlying neurotoxic effects of chemotherapy and potentially related to protective effects of fluoxetine, peripheral markers of inflammatory cytokines will be measured in blood samples drawn at the time of neuroimaging (Specific Aim 3). If use of fluoxetine in cancer patients can be validated in this manner and lead to its adoption in the clinical setting, it will constitute the first drug with demonstrated utility for the prevention of cerebral dysfunction associated with exposure to chemotherapy. Moreover, as this involves an agent that is already FDA-cleared for other indications, widely commercially available throughout the U.S. and other parts of the world, and relatively inexpensive since it is obtainable in generic formulations, it would represent a pharmacologic approach that is amenable to rapid translation to the clinical setting.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Scheduled to undergo chemotherapy, or has completed chemotherapy no more than a month prior to enrollment, for breast cancer or lymphoma
  • Age 21 or above
  • Geographically accessible for follow-up in one year
  • English language proficient
  • Able to provide informed consent

Exclusion Criteria:

  • Pregnant
  • Evidence of current or past disorder/disease of the central nervous system or any medical condition that might be expected to impact cognitive functioning (e.g. multiple sclerosis)
  • History of head trauma with loss of consciousness greater than 30 minutes
  • Epilepsy, dementia, or severe learning disability
  • Current psychotic-spectrum disorder (e.g. schizophrenia, bipolar disorder, major affective disorder) or current substance abuse or dependence
  • History of whole brain irradiation or surgery
  • Active diagnosis of autoimmune disorder e.g., systemic lupus erythematosis, rheumatoid arthritis, vasculitis
  • Insulin dependent diabetes
  • Uncontrolled allergic condition or asthma
  • Chronic use of oral steroid medication
  • Hormone therapy (estrogen, progestin compounds) other than vaginal estrogen
  • Due to the subtleties of neuropsychological test evaluation, including necessity for repeated administration with alternate forms, we must also exclude non-English language proficient subjects.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01615055

Contacts
Contact: Daniel H. Silverman, M.D., Ph.D. 310-825-4257 dsilver@ucla.edu

Locations
United States, California
City of Hope Not yet recruiting
Duarte, California, United States, 91010
Contact: Arti Hurria, M.D.         
UCLA Medical Center Not yet recruiting
Los Angeles, California, United States, 90024
Contact: Daniel H. Silverman    310-825-4257      
Sponsors and Collaborators
University of California, Los Angeles
Beckman Research Institute
Investigators
Principal Investigator: Daniel H. Silverman, M.D., Ph.D. University of California, Los Angeles
  More Information

No publications provided

Responsible Party: Daniel H. Silverman, Professor, Medical and Molecular Pharmacology, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT01615055     History of Changes
Other Study ID Numbers: 12-000568
Study First Received: June 6, 2012
Last Updated: June 7, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:
Chemotherapy
Cognitive
Prozac
Fluoxetine
FDG
PET

Additional relevant MeSH terms:
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Fluoxetine
Antidepressive Agents
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014