Fluoxetine Prevention Trial
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ClinicalTrials.gov Identifier: NCT01615055 |
Recruitment Status
:
Not yet recruiting
First Posted
: June 8, 2012
Last Update Posted
: October 31, 2017
|
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Cognitive Dysfunction | Drug: Fluoxetine Other: Placebo | Early Phase 1 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 376 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Prevention |
Official Title: | Prevention of Cognitive Decline After Chemotherapy, With Fluoxetine Treatment |
Estimated Study Start Date : | June 2018 |
Estimated Primary Completion Date : | October 2020 |
Estimated Study Completion Date : | October 2020 |

Arm | Intervention/treatment |
---|---|
Experimental: Fluoxetine tablets |
Drug: Fluoxetine
20-40 mg fluoxetine po qd for 6 months
Other Name: Prozac
|
Placebo Comparator: Placebo tablets |
Other: Placebo
20-40 mg pharmacologically inactive tablets for 6 months
Other Name: "sugar" pill
|
- Change from baseline in regional cerebral metabolism [ Time Frame: Baseline and 6 months ]
- Durability of the protective effect of fluoxetine [ Time Frame: 6 months and 1 year ]
- Change from baseline in neuropsychological (cognitive, functional) test results [ Time Frame: Baseline, 6 months, and 1 year ]
- Correlation between cognitive functioning and cerebral metabolism by correlating neuropsychological testing results with PET imaging [ Time Frame: Baseline, 6 months, and 1 year ]
- Correlation between inflammatory cytokines and cerebral metabolism by correlating blood cytokine marker levels with PET imaging [ Time Frame: Baseline, 6 months, and 1 year ]

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Ages Eligible for Study: | 21 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01615055
Contact: Daniel H. Silverman, M.D., Ph.D. | 310-825-4257 | dsilver@ucla.edu |
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 |
Principal Investigator: | Daniel H. Silverman, M.D., Ph.D. | University of California, Los Angeles |
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 |
First Posted: | June 8, 2012 Key Record Dates |
Last Update Posted: | October 31, 2017 |
Last Verified: | October 2017 |
Studies a U.S. FDA-regulated Drug Product: | Yes | |
Studies a U.S. FDA-regulated Device Product: | Yes | |
Device Product Not Approved or Cleared by U.S. FDA: | No |
Keywords provided by Daniel H. Silverman, University of California, Los Angeles:
Chemotherapy Cognitive Prozac |
Fluoxetine FDG PET |
Additional relevant MeSH terms:
Fluoxetine Cognitive Dysfunction Cognition Disorders Neurocognitive Disorders Mental Disorders Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action |
Neurotransmitter Agents Serotonin Agents Physiological Effects of Drugs Antidepressive Agents, Second-Generation Antidepressive Agents Psychotropic Drugs Cytochrome P-450 CYP2D6 Inhibitors Cytochrome P-450 Enzyme Inhibitors Enzyme Inhibitors |