Mild Cognitive ImpairmentNCT02608840
Auditory Stimulation of Slow Wave Sleep and Memory in Mild Cognitive Impairment and Older Adults
A study testing Auditory stimulation during sleep in people with Mild Cognitive Impairment, run by Northwestern University at 1 site in United States.
Trial summary
This study will evaluate the ability of sounds played during slow wave sleep using a phase locked loop algorithm to enhance slow wave sleep and memory in cognitively healthy older adults and in those with amnestic mild cognitive impairment. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- Auditory stimulation during sleep
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2015to 31 Dec 2018
- Phase
- Interventional
- 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 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women age ≥60 years;
- Amnestic MCI group: Diagnosis of aMCI based on change in cognition compared to the individual's previous level, impairment of episodic memory, preserved independence in functional abilities, and no evidence of impairment in social or occupational functioning;
- Healthy Older Adults Group: Intact cognitive profile based on neuropsychology testing within 1 standard deviation for age and education status.
- regular reported sleep and wake times
Who cannot join
- moderate-severe sleep apnea defined by apnea-hypopnea index ≥15 events/hour or periodic limb movement index ≥15/hour on the screening home sleep test;
- unstable medical or psychiatric disorder;
- currently doing rotating shift work or night work;
- history of seizures or taking medications that may lower the seizure threshold;
- current use of any sedative/hypnotics or stimulants, gabapentin, pregabalin, tricyclic antidepressants, and trazodone or other psychoactive medications that may alter slow wave sleep; however, stable (3 months or longer) use of antidepressants will be allowed.
- hearing loss
Trial locations and contacts
1 site in 1 country.
About this study
This study will evaluate the ability of sounds played during slow wave sleep using a phase locked loop algorithm to enhance slow wave sleep and memory in cognitively healthy older adults and in those with amnestic mild cognitive impairment.
Read the detailed description
Alzheimer's disease is a degenerative disorder associated with aging and presents a significant human and financial burden. Amnestic mild cognitive impairment (aMCI) is a disorder of impaired memory and is a precursor to Alzheimer's disease. Current treatments are symptomatic and do not slow disease progression. There is increasing evidence linking sleep and cognition, such that decreased sleep, particularly slow wave sleep (physiologically slow wave activity; SWA), is associated with impaired cognitive performance. Not only does SWA decrease with aging, it is much less in people with aMCI than cognitively normal elderly. Interventions that improve sleep may also improve cognition. Auditory stimulation using sounds played through headphones or speakers during sleep have been shown to increase SWA and memory in young adults. Because this method plays sounds at fixed intervals, its ability to enhance SWA may be limited. Investigators have developed an improved method that measures slow waves during sleep in real time and delivers the sound at a particular phase of the slow wave (phase locked loop; PLL). Given that people with aMCI have low SWA, this method may be able to improve cognition by enhancing SWA. Our objective is to determine whether the PLL method of auditory stimulation can increase SWA and improve cognition in people with aMCI. Investigators propose a randomized sham-controlled cross-over study of auditory stimulation that population.
The specific aims are:
- to determine a dose and duration of stimulation required to increase SWA by 10% in people with aMCI;
- to determine the effect of the stimulus on cognitive performance in people with aMCI using word pair recall and the NIH Toolbox cognitive battery, which includes tests in multiple cognitive domains.
Investigators will recruit 15 participants with aMCI identified through the Northwestern University Cognitive Neurology and Alzheimer's Disease Center Clinical Core. Participants will undergo 2 separate nights of polysomnography (stimulation and sham) and cognitive testing on stimulation and sham visits. There will be approximately 1 week between overnight visits. The order of stimulation and sham will be randomized. Results study will be used to determine the optimal stimulation parameters, provide preliminary data on its potential effect, and guide design of future studies.
- Conditions
- Mild Cognitive Impairment
- Being tested
- Auditory stimulation during sleep, Sham Intervention
- Keywords
- slow-wave sleep, cognition, auditory stimulation
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Auditory stimulation during sleepOther
The intervention is a brain computer interface program which measures brain electroencephalogram to identify slow waves and time the sounds. Barely audible sounds are delivered through headphones and played during sleep (specifically, during slow wave sleep).
Sham InterventionOther
The brain electroencephalogram is measured and headphones are worn, but sounds are not played during sleep.
| Study group | Role | What they receive |
|---|---|---|
| MCI auditory stimulation | Experimental | MCI patients receiving auditory stimulation during sleep (crossover arm 1) Receives: Other: Auditory stimulation during sleep |
| MCI sham stimulation | Sham comparator | Sham intervention: MCI patients sleeping with headphones but sounds not played (crossover arm 2) Receives: Other: Sham Intervention |
| Older adult auditory stimulation | Experimental | healthy older adults receiving auditory stimulation during sleep (crossover arm 1) Receives: Other: Auditory stimulation during sleep |
| older adult sham stimulation | Sham comparator | Sham intervention: healthy older adults sleeping with headphones but sounds not played (crossover arm 2) Receives: Other: Sham Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Memory performance on a word pair recall
Participants will initially view word pairs on a computer screen. Participants then complete a recall, where they are presented with one word and freely recall the second word from the pair. Participants complete word pair recall prior to sleep and then again after waking in the morning. This test is completed during both experiment visits.
Measured: Through study completion, approximately 1.5 years.
Secondary outcomes (1)
NIH Cognition Toolbox - Composite score
Participants will complete the NIH toolbox in the morning following both experimental nights. The investigators are evaluating composite scores from the NIH Cognition Toolbox between the two nights.
Measured: Through study completion, approximately 1.5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2015 (estimated)
- Study startJul 2015
- Primary completion31 Dec 2018
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roneil Malkani, Northwestern University
- Investigators
- Roneil G Malkani, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02608840
- Sponsor's protocol ID
- STU00200555
- Status last verified
- Nov 2019
- First submitted
- 6 Nov 2015
- Last updated
- 6 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004 Sep;256(3):183-94. doi: 10.1111/j.1365-2796.2004.01388.x.
PubMed 15324362Born J, Rasch B, Gais S. Sleep to remember. Neuroscientist. 2006 Oct;12(5):410-24. doi: 10.1177/1073858406292647.
PubMed 16957003Mander BA, Rao V, Lu B, Saletin JM, Lindquist JR, Ancoli-Israel S, Jagust W, Walker MP. Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. Nat Neurosci. 2013 Mar;16(3):357-64. doi: 10.1038/nn.3324. Epub 2013 Jan 27.
PubMed 23354332Dijk DJ, Beersma DG, van den Hoofdakker RH. All night spectral analysis of EEG sleep in young adult and middle-aged male subjects. Neurobiol Aging. 1989 Nov-Dec;10(6):677-82. doi: 10.1016/0197-4580(89)90004-3.
PubMed 2628779Van Cauter E, Leproult R, Plat L. Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. JAMA. 2000 Aug 16;284(7):861-8. doi: 10.1001/jama.284.7.861.
PubMed 10938176Ngo HV, Claussen JC, Born J, Molle M. Induction of slow oscillations by rhythmic acoustic stimulation. J Sleep Res. 2013 Feb;22(1):22-31. doi: 10.1111/j.1365-2869.2012.01039.x. Epub 2012 Aug 23.
PubMed 22913273Tononi G, Riedner BA, Hulse BK, Ferrarelli F, Sarasso S. Enhancing sleep slow waves with natural stimuli. Medicamundi 2010;54:73-9.
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Auditory Stimulation of Slow Wave Sleep and Memory in Mild Cognitive Impairment and Older Adults
- ClinicalTrials.gov ID
- NCT02608840
- Acronym / sponsor ID
- STU00200555
- Conditions
- Mild Cognitive Impairment
- Keywords
- slow-wave sleep, cognition, auditory stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 20 Nov 2015 (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.
This study will evaluate the ability of sounds played during slow wave sleep using a phase locked loop algorithm to enhance slow wave sleep and memory in cognitively healthy older adults and in those with amnestic mild cognitive impairment.
Detailed description
Alzheimer's disease is a degenerative disorder associated with aging and presents a significant human and financial burden. Amnestic mild cognitive impairment (aMCI) is a disorder of impaired memory and is a precursor to Alzheimer's disease. Current treatments are symptomatic and do not slow disease progression. There is increasing evidence linking sleep and cognition, such that decreased sleep, particularly slow wave sleep (physiologically slow wave activity; SWA), is associated with impaired cognitive performance. Not only does SWA decrease with aging, it is much less in people with aMCI than cognitively normal elderly. Interventions that improve sleep may also improve cognition. Auditory stimulation using sounds played through headphones or speakers during sleep have been shown to increase SWA and memory in young adults. Because this method plays sounds at fixed intervals, its ability to enhance SWA may be limited. Investigators have developed an improved method that measures slow waves during sleep in real time and delivers the sound at a particular phase of the slow wave (phase locked loop; PLL). Given that people with aMCI have low SWA, this method may be able to improve cognition by enhancing SWA. Our objective is to determine whether the PLL method of auditory stimulation can increase SWA and improve cognition in people with aMCI. Investigators propose a randomized sham-controlled cross-over study of auditory stimulation that population.
The specific aims are:
- to determine a dose and duration of stimulation required to increase SWA by 10% in people with aMCI;
- to determine the effect of the stimulus on cognitive performance in people with aMCI using word pair recall and the NIH Toolbox cognitive battery, which includes tests in multiple cognitive domains.
Investigators will recruit 15 participants with aMCI identified through the Northwestern University Cognitive Neurology and Alzheimer's Disease Center Clinical Core. Participants will undergo 2 separate nights of polysomnography (stimulation and sham) and cognitive testing on stimulation and sham visits. There will be approximately 1 week between overnight visits. The order of stimulation and sham will be randomized. Results study will be used to determine the optimal stimulation parameters, provide preliminary data on its potential effect, and guide design of future studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MCI auditory stimulation | Experimental | Other: Auditory stimulation during sleepMCI patients receiving auditory stimulation during sleep (crossover arm 1) |
| MCI sham stimulation | Sham comparator | Other: Sham InterventionSham intervention: MCI patients sleeping with headphones but sounds not played (crossover arm 2) |
| Older adult auditory stimulation | Experimental | Other: Auditory stimulation during sleephealthy older adults receiving auditory stimulation during sleep (crossover arm 1) |
| older adult sham stimulation | Sham comparator | Other: Sham InterventionSham intervention: healthy older adults sleeping with headphones but sounds not played (crossover arm 2) |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women age ≥60 years;
- Amnestic MCI group: Diagnosis of aMCI based on change in cognition compared to the individual's previous level, impairment of episodic memory, preserved independence in functional abilities, and no evidence of impairment in social or occupational functioning;
- Healthy Older Adults Group: Intact cognitive profile based on neuropsychology testing within 1 standard deviation for age and education status.
- regular reported sleep and wake times
Key exclusion criteria (6 listed)
- moderate-severe sleep apnea defined by apnea-hypopnea index ≥15 events/hour or periodic limb movement index ≥15/hour on the screening home sleep test;
- unstable medical or psychiatric disorder;
- currently doing rotating shift work or night work;
- history of seizures or taking medications that may lower the seizure threshold;
- current use of any sedative/hypnotics or stimulants, gabapentin, pregabalin, tricyclic antidepressants, and trazodone or other psychoactive medications that may alter slow wave sleep; however, stable (3 months or longer) use of antidepressants will be allowed.
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 |
|---|---|---|
| Auditory stimulation during sleepThe intervention is a brain computer interface program which measures brain electroencephalogram to identify slow waves and time the sounds. Barely audible sounds are delivered through headphones and played during sleep (specifically, during slow wave sleep). | Other | MCI auditory stimulation, Older adult auditory stimulation |
| Sham InterventionThe brain electroencephalogram is measured and headphones are worn, but sounds are not played during sleep. | Other | MCI sham stimulation, older adult sham stimulation |
Primary outcome
Memory performance on a word pair recall
Time frame: Through study completion, approximately 1.5 years.
Participants will initially view word pairs on a computer screen. Participants then complete a recall, where they are presented with one word and freely recall the second word from the pair. Participants complete word pair recall prior to sleep and then again after waking in the morning. This test is completed during both experiment visits.
1 secondary outcome
NIH Cognition Toolbox - Composite score
Time frame: Through study completion, approximately 1.5 years.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2019.
- Background: PubMed 15324362Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004 Sep;256(3):183-94. doi: 10.1111/j.1365-2796.2004.01388.x.
- Background: PubMed 16957003Born J, Rasch B, Gais S. Sleep to remember. Neuroscientist. 2006 Oct;12(5):410-24. doi: 10.1177/1073858406292647.
- Background: PubMed 23354332Mander BA, Rao V, Lu B, Saletin JM, Lindquist JR, Ancoli-Israel S, Jagust W, Walker MP. Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. Nat Neurosci. 2013 Mar;16(3):357-64. doi: 10.1038/nn.3324. Epub 2013 Jan 27.
- Background: PubMed 2628779Dijk DJ, Beersma DG, van den Hoofdakker RH. All night spectral analysis of EEG sleep in young adult and middle-aged male subjects. Neurobiol Aging. 1989 Nov-Dec;10(6):677-82. doi: 10.1016/0197-4580(89)90004-3.
- Background: PubMed 10938176Van Cauter E, Leproult R, Plat L. Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. JAMA. 2000 Aug 16;284(7):861-8. doi: 10.1001/jama.284.7.861.
- Background: PubMed 22913273Ngo HV, Claussen JC, Born J, Molle M. Induction of slow oscillations by rhythmic acoustic stimulation. J Sleep Res. 2013 Feb;22(1):22-31. doi: 10.1111/j.1365-2869.2012.01039.x. Epub 2012 Aug 23.
- BackgroundTononi G, Riedner BA, Hulse BK, Ferrarelli F, Sarasso S. Enhancing sleep slow waves with natural stimuli. Medicamundi 2010;54:73-9.
- Individual participant dataSharing planned: No
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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.
Roneil G Malkani, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Auditory stimulation during sleep in people with Mild Cognitive Impairment, run by Northwestern University at 1 site 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 4 inclusion and 6 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: finished, as of the sponsor's last update on 6 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Memory performance on a word pair recall (time frame: Through study completion, approximately 1.5 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02608840, which also lists 7 linked publications.
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 6 Nov 2019.