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

June 6, 2012
June 7, 2012
October 2012
October 2017   (final data collection date for primary outcome measure)
Change from baseline in regional cerebral metabolism [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01615055 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Fluoxetine Prevention Trial
Prevention of Cognitive Decline After Chemotherapy, With Fluoxetine Treatment

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Cognitive Dysfunction
  • Drug: Fluoxetine
    20-40 mg fluoxetine po qd for 6 months
    Other Name: Prozac
  • Drug: Placebo
    same as above with pharmacologically inactive tablets
    Other Name: "sugar" pill
  • Experimental: Fluoxetine tablets
    Intervention: Drug: Fluoxetine
  • Placebo Comparator: Placebo tablets
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
376
October 2017
October 2017   (final data collection date for primary outcome measure)

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.
Both
21 Years and older
No
Contact: Daniel H. Silverman, M.D., Ph.D. 310-825-4257 dsilver@ucla.edu
United States
 
NCT01615055
12-000568
Yes
Daniel H. Silverman, University of California, Los Angeles
University of California, Los Angeles
Beckman Research Institute
Principal Investigator: Daniel H. Silverman, M.D., Ph.D. University of California, Los Angeles
University of California, Los Angeles
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP