Disease Modifying Potential of 5mg of Melatonin on Cognition and Brain Health in Aging

NCT ID: NCT03954899

Last Updated: 2025-03-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

230 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-12

Study Completion Date

2025-11-30

Brief Summary

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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

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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

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Mild Cognitive Impairment Cognitive Decline Healthy Aging

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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MCI+ Melatonin 5mg

MCI+ individuals receiving 5mg of melatonin-OTC for a period of 9 months

Group Type EXPERIMENTAL

melatonin

Intervention Type DIETARY_SUPPLEMENT

5mg of melatonin-otc 30 minutes before sleep

MCI+ placebo

MCI+ individuals receiving placebo for a period of 9 months

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type OTHER

placebo 30 minutes before sleep

MCI- Melatonin 5mg

MCI- individuals receiving 5mg of melatonin-OTC for a period of 9 months

Group Type EXPERIMENTAL

melatonin

Intervention Type DIETARY_SUPPLEMENT

5mg of melatonin-otc 30 minutes before sleep

MCI- placebo

MCI- individuals receiving placebo for a period of 9 months

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type OTHER

placebo 30 minutes before sleep

Interventions

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melatonin

5mg of melatonin-otc 30 minutes before sleep

Intervention Type DIETARY_SUPPLEMENT

placebo

placebo 30 minutes before sleep

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. between ages of 56-85 years
2. all participants must score 18 or above on Montreal Cognitive Assessment (MoCA);
3. all participants must have a clinical dementia rating (CDR) Sum of boxes \<1;
4. need to be willing to undergo CSF LP on two occasions over the course of their participation,
5. 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
6. BMI \< 35 at the time of enrollment
7. 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.

Exclusion Criteria

1. 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.
2. CDR\>=1, clinically significant depression/anxiety (GDS\>=9; GAI\>=9 ),
3. 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).
Minimum Eligible Age

56 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Natalie Denburg

OTHER

Sponsor Role lead

Responsible Party

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Natalie Denburg

Associate Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Natalie Denburg, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

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University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Natalie Denburg, Ph.D

Role: CONTACT

3193846050

Facility Contacts

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Natalie Denburg, Ph.D.

Role: primary

3193846050

Other Identifiers

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1R01AG062673-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

201903824

Identifier Type: -

Identifier Source: org_study_id

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