Mild Cognitive ImpairmentNCT03954899
Disease Modifying Potential of 5mg of Melatonin on Cognition and Brain Health in Aging
A study testing melatonin in people with Mild Cognitive Impairment and Cognitive Decline, run by Natalie Denburg at 1 site in United States.
Trial summary
The study will examine whether 5mg melatonin (over the counter, OTC) over a 9-month period improves Alzheimer's disease (AD) biomarkers and cognitive function in two groups of individuals: those with mild cognitive impairment (MCI+) and those who are not (MCI-). Read more about this study
- Who is it for?
- Ages 56 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment, Cognitive Decline, Healthy Aging
- What is being tested?
- melatonin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 230 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Nov 2019to Feb 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 56 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- between ages of 56-85 years
- all participants must score 18 or above on Montreal Cognitive Assessment (MoCA);
- all participants must have a clinical dementia rating (CDR) Sum of boxes <1;
- need to be willing to undergo CSF LP on two occasions over the course of their participation,
- need to be able and willing to stop using any prescription or non-prescription sleep aids (e.g.(e.g. Ambien, Sonata, Lunesta, Belsomra, Rozerem, Halcion, Intermezzo, Doxepin, Melatonin, etc.) for the duration of the study except for study-issued medications
- BMI < 35 at the time of enrollment
Show all 13Show fewer
- willing to bring a study partner (spouse, child or friend) who knows them well to each of the four visits
- AS OF AUGUST 2024, THE LUMBAR PUNCTURE PROCEDURES FOR THIS CLINICAL TRIAL HAVE BEEN ELIMINATED. THAT IS, PARTICIPANTS ARE NO LONGER RECEIVING A LUMBER PUNCTURE. BUT ARE CONTINUING TO RECEIVE TWO SEPARATE BLOOD DRAWS FOR BIOMARKER TESTING.
- The exclusion criteria are:
- Individuals with any of the following conditions/ diseases will be excluded:
- Obstructive sleep apnea (OSA) without CPAP use, chronic obstructive pulmonary disease, emphysema, major psychiatric disease (bipolar, schizophrenia), history of alcohol/drug abuse, neurodegenerative disease diagnosis (e.g. Parkinson's, Lewy body, ALS, MS), prior history of stroke or traumatic brain injury, have undergone chemotherapy in the past 2 years, have been hospitalized for injury/surgery in the past three-months.
- CDR>=1, clinically significant depression/anxiety (GDS>=9; GAI>=9 ),
- Participants who are on any of the following medications will be excluded: Fluvoxamine (Luvox)/ Fluoxetine (Prozac), Nifedipine (a blood pressure medication), all anti-coagulants (e.g. Warfarin, Coumadin, Heparin, , Lovenox, Xarelto, Pradaxa, etc.), anti-seizure drugs (e.g. Acetazolamide, Carbamazepine, Clobazam, Clonazepam, Gabapentin, etc.), muscle relaxants (e.g.Baclofen, Valium/ diazepam, Flexeril, etc.), or narcotic pain relievers (e.g.Codeine, Tramadol, Hydrocodone, Demerol, etc).
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
Natalie Denburg, Ph.D., 3193846050, natalie-denburg@uiowa.edu
Natalie Denburg, Ph.D.
About this study
Official title: Evaluating the Disease Modifying Potential of a Sleep Intervention on Alzheimer's Disease (AD) Biomarkers
The study will examine whether 5mg melatonin (over the counter, OTC) over a 9-month period improves Alzheimer's disease (AD) biomarkers and cognitive function in two groups of individuals: those with mild cognitive impairment (MCI+) and those who are not (MCI-). AD biomarkers will be measured from cerebrospinal fluid (CSF) obtained from lumbar punctures. Cognitive function will be evaluated with routine neuropsychological tests.
AS OF AUGUST 2024, THE LUMBAR PUNCTURE PROCEDURES FOR THIS CLINICAL TRIAL HAVE BEEN ELIMINATED. THAT IS, PARTICIPANTS ARE NO LONGER RECEIVING A LUMBER PUNCTURE. BUT ARE CONTINUING TO RECEIVE TWO SEPARATE BLOOD DRAWS FOR BIOMARKER TESTING.
Read the detailed description
To address these broad aims, participants will be recruited from the Neuropsychology Clinic, community, Alzheimer's association local chapter events and support groups, senior citizen centers. Following fulfillment of several inclusionary and exclusionary criteria online/on the phone, participants will first complete a baseline visit with several tests designed to measure aspects of motor, affective, and cognitive function. The baseline visit will be briefer for those who do not fulfill in-person components of the inclusionary/exclusionary criteria (BMI<35; MoCA>=18; and CDR <=.5).
Based on the information obtained during the baseline visit, participants' cognitive status will be categorized as either MCI+ or MCI-. The criteria adopted in this study for a determination of MCI is less stringent than typical clinical criteria. This information will be used to conduct stratified randomization of participants to placebo or active (5mg melatonin) arms. The schedule of randomization will be determined by University of Iowa Hospital \& Clinic's pharmacy so that study personnel and participants will not know which participant has been assigned to which study arm.
At the end of the baseline visit, participants will be given actigraphy watches to wear for a period of 8 weeks, a wash-out phase; phase#1. The watches monitor sleep and circadian rhythm in each participant's daily life. At the end of 8 weeks, participants will return to the lab to complete a brief battery of cognitive tests. At the end of the visit, they will be given freshly charged actigraphy watches to take home with them until week-16 as well as the first supply of study issued medications (beginning phase#2 of the study). They will receive a phone call at the beginning of week-9 to complete brief questionnaires regarding sleep quality, mood, and any physical symptoms that may be associated with study-issued medications. At the week-16 visit, the participants will return their actigraphy watches, complete brief cognitive testing, questionnaires on sleep quality, mood, physical symptoms that may be associated with study-issued medications, and complete the first LP and blood draw. They will also be given their supply of study-issued medications for the next 7-month period. They will receive a phone call around week-30 (midway between week-16 and the final study visit of week-44) to inquire about sleep quality, any physical symptoms that may be associated with study-issued medications, and mood. The final study visit will take place on week-44. The visit will be very similar to the baseline visit and will include comprehensive cognitive testing, questionnaires, and an LP. Participants will also receive a phone call the day after each LP to query them about any discomfort they may be experiencing and the adequacy of over-the-counter pain medications in addressing it.
In addition to these procedures, participants will be asked to consent to banking of CSF for assaying of future biomarkers during the two study LPs.
AS OF AUGUST 2024, THE LUMBAR PUNCTURE PROCEDURES FOR THIS CLINICAL TRIAL HAVE BEEN ELIMINATED. THAT IS, PARTICIPANTS ARE NO LONGER RECEIVING A LUMBER PUNCTURE. BUT ARE CONTINUING TO RECEIVE TWO SEPARATE BLOOD DRAWS AT WEEKS 8 AND 44 FOR BIOMARKER TESTING.
- Conditions
- Mild Cognitive Impairment, Cognitive Decline, Healthy Aging
- Being tested
- melatonin, placebo
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
melatoninDietary supplement
5mg of melatonin-otc 30 minutes before sleep
placeboOther
placebo 30 minutes before sleep
| Study group | Role | What they receive |
|---|---|---|
| MCI+ Melatonin 5mg | Experimental | MCI+ individuals receiving 5mg of melatonin-OTC for a period of 9 months Receives: Dietary Supplement: melatonin |
| MCI+ placebo | Placebo comparator | MCI+ individuals receiving placebo for a period of 9 months Receives: Other: placebo |
| MCI- Melatonin 5mg | Experimental | MCI- individuals receiving 5mg of melatonin-OTC for a period of 9 months Receives: Dietary Supplement: melatonin |
| MCI- placebo | Placebo comparator | MCI- individuals receiving placebo for a period of 9 months Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Episodic memory
Composite episodic memory performance scores will be computed based on the following tests: Auditory Verbal Learning Test (AVLT), Free \& Cued Selective Reminding Test (FCSRT), Repeatable Battery for the Assessment of Neuropsychological Status (Story memory) at the week-8, week-16, and week-44 visits. Alternate forms will be used to assess performance in each of these tests across these visits to minimize practice effects. Composite scores at week-16 and week-44 visits will reference the pretreatment group mean and standard deviations to permit the detection of deviation from pre-treatment levels.
Measured: Assessed at pre-treatment (week-8), and two post-treatment occasions: week-16 and week-44.
Secondary outcomes (6)
Overall cognitive function
Composite performance scores will be computed based on the following cognitive tests: AVLT, FCSRT, RBANS-Story, Benton Visual Retention Test (BVRT), Trail Making Test (PartsA\&B), and Controlled Oral Word Association (COWA) at the week-8, week-16, and week-44 visits. Alternate forms will be used to assess performance in each of these tests, when available, across these visits to minimize practice effects. Composite scores at week-16 and week-44 visits will reference the pretreatment group mean and standard deviations to permit the detection of deviation from pre-treatment levels.
Measured: Assessed at pre-treatment (week-8), and two post-treatment occasions: week-16 and week-44.
p-tau/Aβ42 ratio
Cerebrospinal values from lumbar puncture
Measured: Assessed at pre-treatment (week-8) and one post-treatment occasion (week-44)
t-tau
Cerebrospinal values from lumbar puncture
Measured: Assessed at pre-treatment (week-8) and one post-treatment occasion (week-44)
Sleep Efficiency
Daily Sleep efficiency values obtained from actigraphy during the wash-out period (weeks 1 to 8) and sleep efficiency values obtained from actigraphy during week-8 to week-16 when participants are on placebo or the active arm.
Measured: Daily from actigraphy in the pre-treatment phase which lasts 8 weeks (phase#1) and daily from actigraphy in the post-treatment phase from week-9 to week-16 (phase#2).
Amplitude (Mesor) of rest-activity rhythm
The 30-second activity counts from actigraphy watches will be submitted to cosinor curve analyses to permit the extraction of peak amplitude per day in both phases of the study (wash-out pre-treatment from week-1 to week-8 and week-9 to week-16 post treatment, phase#2). These amplitude values will be averaged to characterize typical amplitude for each participant within each study phase.
Measured: Daily from actigraphy in the pre-treatment phase which lasts 8 weeks (phase#1) and daily from actigraphy in the post-treatment phase from week-9 to week-16 (phase#2).
Acrophase of rest-activity rhythm
The 30-second activity counts from actigraphy watches will be submitted to cosinor curve analyses to permit the extraction of the time of day at peak amplitude per day in both phases of the study (wash-out pre-treatment from week-1 to week-8 and week-9 to week-16 post treatment, phase#2). These acrophase values will be averaged to characterize typical timing of peak amplitude for each participant within each study phase.
Measured: Daily from actigraphy in the pre-treatment phase which lasts 8 weeks (phase#1) and daily from actigraphy in the post-treatment phase from week-9 to week-16 (phase#2).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2019
- Study start12 Nov 2019
- Primary completionFeb 2028 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Natalie Denburg
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Natalie Denburg, University of Iowa
- Investigators
- Natalie Denburg, Ph.D., Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03954899
- Sponsor's protocol ID
- 201903824
- Other IDs
- 1R01AG062673-01
- Status last verified
- Sep 2026
- First submitted
- 15 May 2019
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Disease Modifying Potential of a Sleep Intervention on Alzheimer's Disease (AD) Biomarkers
- ClinicalTrials.gov ID
- NCT03954899
- Acronym / sponsor ID
- 201903824
- Conditions
- Mild Cognitive Impairment, Cognitive Decline, Healthy Aging
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 230 participants (estimated)
- Lead sponsor
- Natalie DenburgUniversity, hospital or other
- Study start
- 12 Nov 2019 (actual)
- Primary completion
- Feb 2028 (estimated)
- Study completion
- Feb 2028 (estimated)
- First posted
- 17 May 2019 (actual)
- 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.
The study will examine whether 5mg melatonin (over the counter, OTC) over a 9-month period improves Alzheimer's disease (AD) biomarkers and cognitive function in two groups of individuals: those with mild cognitive impairment (MCI+) and those who are not (MCI-). AD biomarkers will be measured from cerebrospinal fluid (CSF) obtained from lumbar punctures. Cognitive function will be evaluated with routine neuropsychological tests.
AS OF AUGUST 2024, THE LUMBAR PUNCTURE PROCEDURES FOR THIS CLINICAL TRIAL HAVE BEEN ELIMINATED. THAT IS, PARTICIPANTS ARE NO LONGER RECEIVING A LUMBER PUNCTURE. BUT ARE CONTINUING TO RECEIVE TWO SEPARATE BLOOD DRAWS FOR BIOMARKER TESTING.
Detailed description
To address these broad aims, participants will be recruited from the Neuropsychology Clinic, community, Alzheimer's association local chapter events and support groups, senior citizen centers. Following fulfillment of several inclusionary and exclusionary criteria online/on the phone, participants will first complete a baseline visit with several tests designed to measure aspects of motor, affective, and cognitive function. The baseline visit will be briefer for those who do not fulfill in-person components of the inclusionary/exclusionary criteria (BMI<35; MoCA>=18; and CDR <=.5).
Based on the information obtained during the baseline visit, participants' cognitive status will be categorized as either MCI+ or MCI-. The criteria adopted in this study for a determination of MCI is less stringent than typical clinical criteria. This information will be used to conduct stratified randomization of participants to placebo or active (5mg melatonin) arms. The schedule of randomization will be determined by University of Iowa Hospital \& Clinic's pharmacy so that study personnel and participants will not know which participant has been assigned to which study arm.
At the end of the baseline visit, participants will be given actigraphy watches to wear for a period of 8 weeks, a wash-out phase; phase#1. The watches monitor sleep and circadian rhythm in each participant's daily life. At the end of 8 weeks, participants will return to the lab to complete a brief battery of cognitive tests. At the end of the visit, they will be given freshly charged actigraphy watches to take home with them until week-16 as well as the first supply of study issued medications (beginning phase#2 of the study). They will receive a phone call at the beginning of week-9 to complete brief questionnaires regarding sleep quality, mood, and any physical symptoms that may be associated with study-issued medications. At the week-16 visit, the participants will return their actigraphy watches, complete brief cognitive testing, questionnaires on sleep quality, mood, physical symptoms that may be associated with study-issued medications, and complete the first LP and blood draw. They will also be given their supply of study-issued medications for the next 7-month period. They will receive a phone call around week-30 (midway between week-16 and the final study visit of week-44) to inquire about sleep quality, any physical symptoms that may be associated with study-issued medications, and mood. The final study visit will take place on week-44. The visit will be very similar to the baseline visit and will include comprehensive cognitive testing, questionnaires, and an LP. Participants will also receive a phone call the day after each LP to query them about any discomfort they may be experiencing and the adequacy of over-the-counter pain medications in addressing it.
In addition to these procedures, participants will be asked to consent to banking of CSF for assaying of future biomarkers during the two study LPs.
AS OF AUGUST 2024, THE LUMBAR PUNCTURE PROCEDURES FOR THIS CLINICAL TRIAL HAVE BEEN ELIMINATED. THAT IS, PARTICIPANTS ARE NO LONGER RECEIVING A LUMBER PUNCTURE. BUT ARE CONTINUING TO RECEIVE TWO SEPARATE BLOOD DRAWS AT WEEKS 8 AND 44 FOR BIOMARKER TESTING.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MCI+ Melatonin 5mg | Experimental | Dietary Supplement: melatoninMCI+ individuals receiving 5mg of melatonin-OTC for a period of 9 months |
| MCI+ placebo | Placebo comparator | Other: placeboMCI+ individuals receiving placebo for a period of 9 months |
| MCI- Melatonin 5mg | Experimental | Dietary Supplement: melatoninMCI- individuals receiving 5mg of melatonin-OTC for a period of 9 months |
| MCI- placebo | Placebo comparator | Other: placeboMCI- individuals receiving placebo for a period of 9 months |
Who may qualify
- Ages
- 56 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- between ages of 56-85 years
- all participants must score 18 or above on Montreal Cognitive Assessment (MoCA);
- all participants must have a clinical dementia rating (CDR) Sum of boxes <1;
- need to be willing to undergo CSF LP on two occasions over the course of their participation,
- need to be able and willing to stop using any prescription or non-prescription sleep aids (e.g.(e.g. Ambien, Sonata, Lunesta, Belsomra, Rozerem, Halcion, Intermezzo, Doxepin, Melatonin, etc.) for the duration of the study except for study-issued medications
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| melatonin5mg of melatonin-otc 30 minutes before sleep | Dietary supplement | MCI+ Melatonin 5mg, MCI- Melatonin 5mg |
| placeboplacebo 30 minutes before sleep | Other | MCI+ placebo, MCI- placebo |
Primary outcome
Episodic memory
Time frame: Assessed at pre-treatment (week-8), and two post-treatment occasions: week-16 and week-44.
Composite episodic memory performance scores will be computed based on the following tests: Auditory Verbal Learning Test (AVLT), Free \& Cued Selective Reminding Test (FCSRT), Repeatable Battery for the Assessment of Neuropsychological Status (Story memory) at the week-8, week-16, and week-44 visits. Alternate forms will be used to assess performance in each of these tests across these visits to minimize practice effects. Composite scores at week-16 and week-44 visits will reference the pretreatment group mean and standard deviations to permit the detection of deviation from pre-treatment levels.
6 secondary outcomes
Overall cognitive function
Time frame: Assessed at pre-treatment (week-8), and two post-treatment occasions: week-16 and week-44.
p-tau/Aβ42 ratio
Time frame: Assessed at pre-treatment (week-8) and one post-treatment occasion (week-44)
t-tau
Time frame: Assessed at pre-treatment (week-8) and one post-treatment occasion (week-44)
Sleep Efficiency
Time frame: Daily from actigraphy in the pre-treatment phase which lasts 8 weeks (phase#1) and daily from actigraphy in the post-treatment phase from week-9 to week-16 (phase#2).
Amplitude (Mesor) of rest-activity rhythm
Time frame: Daily from actigraphy in the pre-treatment phase which lasts 8 weeks (phase#1) and daily from actigraphy in the post-treatment phase from week-9 to week-16 (phase#2).
Acrophase of rest-activity rhythm
Time frame: Daily from actigraphy in the pre-treatment phase which lasts 8 weeks (phase#1) and daily from actigraphy in the post-treatment phase from week-9 to week-16 (phase#2).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2026.
- Individual participant dataSharing planned: No
Related trials for Mild Cognitive Impairment
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingObservational study
Community-based Screening for Alzheimer's Disease
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
RecruitingObservational study
InRAD Observational Study
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
Recruiting
Treating Insomnia in Mild Cognitive Impairment
Mild Cognitive Impairment (MCI), Insomnia
Recruiting
Telehealth-Adapted Compensatory Training and Intervention for Cognition
MCI, Mild Cognitive Impairment
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.
Natalie Denburg, Ph.D. principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing melatonin in people with Mild Cognitive Impairment and Cognitive Decline, run by Natalie Denburg 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 13 inclusion and 0 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: looking for participants now, as of the sponsor's last update on 28 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Natalie Denburg, Ph.D (3193846050, natalie-denburg@uiowa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Episodic memory (time frame: Assessed at pre-treatment (week-8), and two post-treatment occasions: week-16 and week-44.). 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 28 Sep 2026.