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History of Changes for Study: NCT03954899
Disease Modifying Potential of 5mg of Melatonin on Cognition and Brain Health in Aging
Latest version (submitted February 10, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 May 15, 2019 None (earliest Version on record)
2 September 4, 2019 Study Status and Eligibility
3 September 29, 2019 Recruitment Status, Study Status, Contacts/Locations and Oversight
4 January 27, 2020 Study Status
5 February 10, 2022 Contacts/Locations, Sponsor/Collaborators, Eligibility, Study Status, Outcome Measures and Study Description
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Study NCT03954899
Submitted Date:  May 15, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: 201903824
Brief Title: Disease Modifying Potential of 5mg of Melatonin on Cognition and Brain Health in Aging
Official Title: Evaluating the Disease Modifying Potential of a Sleep Intervention on Alzheimer's Disease (AD) Biomarkers
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2019
Overall Status: Not yet recruiting
Study Start: July 2019
Primary Completion: July 2023 [Anticipated]
Study Completion: July 2023 [Anticipated]
First Submitted: May 15, 2019
First Submitted that
Met QC Criteria:
May 15, 2019
First Posted: May 17, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
May 15, 2019
Last Update Posted: May 17, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Nazan Aksan
Responsible Party: Sponsor-Investigator
Investigator: Nazan Aksan
Official Title: Research Assistant Professor
Affiliation: University of Iowa
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.
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<30; 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, they will be return to the lab to complete a brief battery of cognitive tests and complete the first lumbar puncture (LPs). 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. The week-16 visit will be very similar to week-8 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 second LP. 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 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 three study LPs.

Open or close this module Conditions
Conditions: Mild Cognitive Impairment
Cognitive Decline
Healthy Aging
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Prevention
Study Phase: Not Applicable
Interventional Study Model: Parallel Assignment
Number of Arms: 4
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 230 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: MCI+ Melatonin 5mg
MCI+ individuals receiving 5mg of melatonin-OTC for a period of 9 months
Dietary Supplement: melatonin
5mg of melatonin-otc 30 minutes before sleep
Placebo Comparator: MCI+ placebo
MCI+ individuals receiving placebo for a period of 9 months
placebo
placebo 30 minutes before sleep
Experimental: MCI- Melatonin 5mg
MCI- individuals receiving 5mg of melatonin-OTC for a period of 9 months
Dietary Supplement: melatonin
5mg of melatonin-otc 30 minutes before sleep
Placebo Comparator: MCI- placebo
MCI- individuals receiving placebo for a period of 9 months
placebo
placebo 30 minutes before sleep
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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.
Secondary Outcome Measures:
1. Overall cognitive function
[ Time Frame: Assessed at pre-treatment (week-8), and two post-treatment occasions: week-16 and week-44. ]

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.
2. p-tau/Aβ42 ratio
[ Time Frame: Assessed at pre-treatment (week-8), and two post-treatment occasions: week-16 and week-44. ]

Cerebrospinal values from lumbar puncture
3. t-tau
[ Time Frame: Assessed at pre-treatment (week-8), and two post-treatment occasions: week-16 and week-44. ]

Cerebrospinal values from lumbar puncture
4. 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). ]

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.
5. 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). ]

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.
6. 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). ]

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.
Open or close this module Eligibility
Minimum Age: 60 Years
Maximum Age: 80 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: Yes
Criteria:

Inclusion Criteria:

  1. between ages of 60-80 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 three occasions over the course of their participation,
  5. need to be able and willing to stop using any prescription or non-prescription sleep aids (i.e.(Ambien, Sonata, Lunesta, Belsomra, Rozerem, Halcion, Intermezzo, Doxepin, melatonin) for the duration of the study except for study-issued medications
  6. BMI < 30 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

The exclusion criteria are:

  1. Individuals with any of the following conditions/ diseases will be excluded:

    Obstructive sleep apnea (OSA), chronic obstructive pulmonary disease, emphysema, major psychiatric disease (bipolar, schizophrenia), history of alcohol/drug abuse, neurodegenerative diseases (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), Warfarin/Coumadin (anti-coagulants), certain azole antifungals (Ketoconazole, Fluconazole), Rifampin/cipro (antibiotics used to treat certain bacterial infections), anti-seizure drugs (e.g. Acetazolamide, Carbamazepine, Clobazam, Clonazepam, Gabapentin), muscle relaxants, or narcotic pain relievers.
Open or close this module Contacts/Locations
Central Contact Person: nazan aksan, phd
Telephone: 3193568112 Ext. 3193568112
Email: nazan-aksan@uiowa.edu
Central Contact Backup: nazan aksan
Telephone: 3193568112 Ext. 3193568112
Email: nazan-aksan@uiowa.edu
Study Officials: nazan aksan
Principal Investigator
University of Iowa
Locations: United States, Iowa
University of Iowa Hospitals & Clinics
Iowa City, Iowa, United States, 52242
Contact:Contact: nazan aksan 319-356-8112 nazan-aksan@uiowa.edu
Contact:Principal Investigator: nazan aksan
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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