Clarithromycin Mechanisms in Hypersomnia Syndromes

NCT04026958 | Completed Phase 2 FDA Drug

• 2 other identifiers: IRB001086811R01NS111280
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate a medication called clarithromycin for treating sleepiness in narcolepsy and idiopathic hypersomnia. Studies have shown that clarithromycin can reduce sleepiness, but researchers do not know how clarithromycin does this. This study will look at brain activity (on magnetic resonance imaging \[MRI\]), inflammation, bacteria living in the gut, and cerebrospinal fluid, to better understand how clarithromycin can reduce sleepiness. This study will recruit 92 participants who will be randomized to receive clarithromycin or a placebo for 14 days.

Conditions

Narcolepsy Without Cataplexy; Idiopathic Hypersomnia; Narcolepsy With Cataplexy

Keywords

Neurology

Outcome Measures

Primary Outcomes (6)

• Change in Epworth Sleepiness Scale Score

  The Epworth Sleepiness Scale asks participants to respond to 8 scenarios with how likely they are to fall asleep on a 4-point scale where 0 = "would never doze" and 3 = "high chance of dozing". Total scores range from 0 to 24 where higher scores indicate a higher chance of falling asleep during daytime activities.

  Day -1, Day 14

• Change in Maintenance of Wakefulness Test (MWT)

  The MWT polysomnographic procedure examines how well participants stay awake during several trials where participants relax in a quiet room for 40 minutes. One study found the mean sleep latency among persons without a sleep disorder to be 35.2 minutes. Sleep latency is compared between study arms.

  Day -1, Day 14

• Change in gamma-aminobutyric acid receptor A (GABA-A) potentiation

  Cerebrospinal fluid (CSF) is drawn to determine the change in levels of GABA-A potentiation between the study arms. The difference between measured current with GABA alone and the current measured with GABA + CSF yields a measure of potentiation for each CSF sample in each condition.

  Day -1, Day 14

• Change in Default Mode Network (DMN) Connectivity

  The default mode network (DMN) consists of a group of highly correlated brain regions most active during quiet rest. DMN connectivity changes with sleep states and it is increasingly implicated in the symptomatology of sleepiness. During resting state, sleep deprived participants demonstrate reduced static connectivity with the DMN. Changes in DMN between the Baseline 1 and Day 13 visits are compared between treatment groups, particularly using quasi-periodic patterns (QPPs), which interrogate network-level connectivity on a dynamic scale. Preservation of the temporal dimension provides more insight into how this spatiotemporal network propagates across condition and pathology.

  Day -2, Day 13

• Change in tumor necrosis factor - alpha (TNF-α)

  Blood samples are used to determine the change in levels of TNF-α between the study arms. TNF-α is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.

  Day -1, Day 14

• Change in gastrointestinal microbiome composition

  Changes in microbiome composition via 16S ribosomal ribonucleic acid (rRNA) sequencing results are compared between study arms.

  Day -1, Day 14

Secondary Outcomes (18)

• On-Treatment Sleep Duration

  Day -1, Day 14

• Change in Fatigue Severity Scale (FSS) Score

  Day -1, Day 14

• Change in Multidimensional Fatigue Inventory (MFI-20) Score

  Day -1, Day 14

• Change in Sleep Inertia Questionnaire (SIQ) Score

  Day -1, Day 14

• On-Treatment Sleep Inertia Likert Scale

  Day -1, Day 14

Study Arms (2)

Clarithromycin

EXPERIMENTAL

Participants in this study arm will receive clarithromycin for 14 days.

Drug: Clarithromycin

Placebo

PLACEBO COMPARATOR

Participants in this study arm will receive a placebo to match clarithromycin for 14 days.

Drug: Placebo

Interventions

Clarithromycin DRUG

Clarithromycin will be dosed as 500 mg twice daily, once upon awakening and once with lunch, for 14 days.

Also known as: Biaxin

Clarithromycin

Placebo DRUG

A placebo to match clarithromycin will be dosed as 500 mg twice daily, once upon awakening and once with lunch, for 14 days.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• diagnosis of idiopathic hypersomnia or narcolepsy
• age 18-60
• free of wake-promoting medication, sleepy despite current wake-promoting medications, or willing to discontinue current wake-promoting medication for at least 5 half-lives prior to baseline measures

You may not qualify if:

• other potential causes of hypersomnolence, including untreated moderate or severe sleep apnea, severe periodic limb movement disorder with arousals, uncontrolled metabolic disorders
• contraindication to clarithromycin
• contraindication to any of the study procedures

Sponsors & Collaborators

• Emory University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Emory Sleep Center

Atlanta, Georgia, 30329, United States

Location

MeSH Terms

Conditions

Idiopathic Hypersomnia; Narcolepsy

Interventions

Clarithromycin

Condition Hierarchy (Ancestors)

Disorders of Excessive Somnolence; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Lynn Marie Trotti, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 19, 2019
• Study Start: September 4, 2019
• Primary Completion: June 18, 2025
• Study Completion: June 18, 2025
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available for sharing beginning 3 months after article publication and ending 3 years after article publication. Reasonable attempts will be made to accommodate requests after 3 years.
• Access Criteria: Individual participant data will be available for sharing with researchers who provide a methodologically sound proposal, and with other entities who provide a clear rationale for data use. Data will be shared for analyses to achieve the aims of the approved proposal. Proposals for using the data should be directed to lbecke2@emory.edu.

Locations

US (1)