NCT03954899

Brief 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-). 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
230

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Nov 2019

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 15, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 17, 2019

Completed
6 months until next milestone

Study Start

First participant enrolled

November 12, 2019

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2025

Completed
Last Updated

March 4, 2025

Status Verified

February 1, 2025

Enrollment Period

6 years

First QC Date

May 15, 2019

Last Update Submit

February 27, 2025

Conditions

Mild Cognitive ImpairmentCognitive DeclineHealthy Aging

Outcome Measures

Primary Outcomes (1)

  • 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.

    Assessed at pre-treatment (week-8), and two post-treatment occasions: week-16 and week-44.

Secondary Outcomes (6)

  • Overall cognitive function

    Assessed at pre-treatment (week-8), and two post-treatment occasions: week-16 and week-44.

  • p-tau/Aβ42 ratio

    Assessed at pre-treatment (week-8) and one post-treatment occasion (week-44)

  • t-tau

    Assessed at pre-treatment (week-8) and one post-treatment occasion (week-44)

  • Sleep Efficiency

    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

    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).

  • +1 more secondary outcomes

Study Arms (4)

MCI+ Melatonin 5mg

EXPERIMENTAL

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

Dietary Supplement: melatonin

MCI+ placebo

PLACEBO COMPARATOR

MCI+ individuals receiving placebo for a period of 9 months

Other: placebo

MCI- Melatonin 5mg

EXPERIMENTAL

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

Dietary Supplement: melatonin

MCI- placebo

PLACEBO COMPARATOR

MCI- individuals receiving placebo for a period of 9 months

Other: placebo

Interventions

melatoninDIETARY_SUPPLEMENT

5mg of melatonin-otc 30 minutes before sleep

MCI+ Melatonin 5mgMCI- Melatonin 5mg
placeboOTHER

placebo 30 minutes before sleep

MCI+ placeboMCI- placebo

Eligibility Criteria

Age56 Years - 85 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Cognition DisordersNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

TryptaminesIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Natalie Denburg, Ph.D.

    University of Iowa

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalie Denburg, Ph.D

CONTACT

3193846050natalie-denburg@uiowa.edu

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

May 15, 2019

First Posted

May 17, 2019

Study Start

November 12, 2019

Primary Completion

November 1, 2025

Study Completion

November 1, 2025

Last Updated

March 4, 2025

Record last verified: 2025-02

Data Sharing

IPD Sharing
Will not share

Locations

US(1)