Cognitive DysfunctionEarly Phase 1NCT01615055
Fluoxetine Prevention Trial
A Early Phase 1 study testing Fluoxetine in people with Cognitive Dysfunction, run by University of California, Los Angeles at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Cognitive Dysfunction
- What is being tested?
- Fluoxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2018to Oct 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
City of Hope
Duarte, California, 91010
UCLA Medical Center
Los Angeles, California, 90024
About this study
Official title: 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.
Read the 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.
- Conditions
- Cognitive Dysfunction
- Being tested
- Fluoxetine, Placebo
- Keywords
- Chemotherapy, Cognitive, Prozac, Fluoxetine, FDG, PET
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluoxetineDrug
Also called Prozac
20-40 mg fluoxetine po qd for 6 months
PlaceboOther
Also called "sugar" pill
20-40 mg pharmacologically inactive tablets for 6 months
| Study group | Role | What they receive |
|---|---|---|
| Fluoxetine tablets | Experimental | Not described Receives: Drug: Fluoxetine |
| Placebo tablets | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in regional cerebral metabolism
Measured: Baseline and 6 months
Secondary outcomes (4)
Durability of the protective effect of fluoxetine
Measured: 6 months and 1 year
Change from baseline in neuropsychological (cognitive, functional) test results
Measured: Baseline, 6 months, and 1 year
Correlation between cognitive functioning and cerebral metabolism by correlating neuropsychological testing results with PET imaging
Measured: Baseline, 6 months, and 1 year
Correlation between inflammatory cytokines and cerebral metabolism by correlating blood cytokine marker levels with PET imaging
Measured: Baseline, 6 months, and 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2012 (estimated)
- Study startJun 2018 (estimated)
- Primary completionOct 2020 (estimated)
- Study completionOct 2020 (estimated)
Why it stopped: Study withdrawn. No participants enrolled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive DysfunctionStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- City of Hope Medical Center
- Responsible party
- Principal investigator, Daniel H. Silverman, University of California, Los Angeles
- Investigators
- Daniel H. Silverman, M.D., Ph.D., Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01615055
- Sponsor's protocol ID
- 12-000568
- Status last verified
- Oct 2018
- First submitted
- 6 Jun 2012
- Last updated
- 15 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Cognitive Decline After Chemotherapy, With Fluoxetine Treatment
- ClinicalTrials.gov ID
- NCT01615055
- Acronym / sponsor ID
- 12-000568
- Conditions
- Cognitive Dysfunction
- Keywords
- Chemotherapy, Cognitive, Prozac, Fluoxetine, FDG, PET
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study withdrawn. No participants enrolled.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- City of Hope Medical Center
- Study start
- Jun 2018 (estimated)
- Primary completion
- Oct 2020 (estimated)
- Study completion
- Oct 2020 (estimated)
- First posted
- 8 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fluoxetine tablets | Experimental | Drug: Fluoxetine |
| Placebo tablets | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FluoxetineAlso: Prozac20-40 mg fluoxetine po qd for 6 months | Drug | Fluoxetine tablets |
| PlaceboAlso: "sugar" pill20-40 mg pharmacologically inactive tablets for 6 months | Other | Placebo tablets |
Primary outcome
Change from baseline in regional cerebral metabolism
Time frame: Baseline and 6 months
4 secondary outcomes
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel H. Silverman, M.D., Ph.D. principal investigator
University of California, Los Angeles
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Fluoxetine in people with Cognitive Dysfunction, run by University of California, Los Angeles at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in regional cerebral metabolism (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2018.