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

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

Narcolepsy Without Cataplexy

Idiopathic Hypersomnia

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

Clarithromycin

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

Placebo

Emory Sleep Center

Clarithromycin Mechanisms in Hypersomnia Syndromes

Antibiotic-mediated Improvements in Vigilance: Mechanisms of Action of Clarithromycin in Hypersomnia Syndromes

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.

The MWT polysomnographic procedure examining 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 will be compared between study arms.

Cerebrospinal fluid (CSF) will be 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 will yield a measure of potentiation for each CSF sample in each condition.

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 connectivity with the DMN. Changes in DMN between the Baseline 1 and Day 13 visits will be compared between treatment groups.

Blood will be drawn 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.

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

Participants will log when they go to bed and when they wake up in order to calculate the number of minutes spent sleeping. Duration of sleep will be compared between study arms.

Fatigue severity will be measured with the Fatigue Severity Scale (FSS). The FSS is a 9-item instrument where responses are on a scale of 1 to 7 where 1 = "disagree" and 7 = "agree". Total scores range from 9 to 63 where higher scores indicate greater fatigue.

The MFI-20 is a 20-item instrument assessing fatigue severity. Responses are on a 5-point scale where 1 = "yes, that is true" and 5 = "no, that is not true". Positively phrased items are reverse scored so that the total score ranges from 20 to100 where higher scores indicate greater severity of fatigue.

The SIQ is an instrument with 21 items with responses on a 5-point scale where 1 = "not at all" and 5 = "all the time". Two additional questions relate to how much time it takes for the respondent to wake up in the morning. Total scores range from 21 to 105 and higher scores indicate increased difficulty from tiredness.

Sleep inertia will be measured with a single item on a 10-point Likert scale asking participants how difficult it was for them to wake up in the morning, were 1 = "not difficult at all" and 10 = "very difficult".

The IHSS is a 14-item instrument assessing symptoms, consequences, and treatment of hypersomnia. Items are scored on a 4 or 5-point scale (depending on severity) and total scores range from 0 to 50, with higher scores indicating more symptoms of hypersomnia.

Blood will be drawn to determine the change in levels of IL-1α between the study arms. IL-1α is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.

Blood will be drawn to determine the change in levels of IL-1β between the study arms. IL-1β is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.

Blood will be drawn to determine the change in levels of IL-2 between the study arms. IL-2 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.

Blood will be drawn to determine the change in levels of IL-6 between the study arms. IL-6 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.

Blood will be drawn to determine the change in levels of IL-8 between the study arms. IL-8 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.

Blood will be drawn to determine the change in levels of IL-15 between the study arms. IL-15 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.

Blood will be drawn to determine the change in levels of IL-18 between the study arms. IL-18 is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.

Blood will be drawn to determine the change in levels of TNF-β between the study arms. TNF-β is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.

Blood will be drawn to determine the change in levels of INF-α between the study arms. INF-α is a soporific cytokine and a reduction in soporific cytokines is hypothesized to reduce daytime sleepiness.

After de-identification, individual patient data collected during the trial that underlie the results reported in the article will be available to be shared with other researchers.

Lynn Marie Trotti

Associate Professor

Emory University

National Institute of Neurological Disorders and Stroke (NINDS)

rifaximin 550 milligrams (mg) orally twice daily for 3 months

Alzheimer's Disease

Rifaximin (Xifaxan, Salix Pharmaceuticals, Bridgewater, N.J.) (See Package Insert) is a drug that is approved by the FDA for use in humans for the treatment of Hepatic Encephalopathy, Traveler's Diarrhea and Irritable Bowel Syndrome. It is commercially available. It will be used in accordance with approved labeling as pertains to dosage and administration for Hepatic Encephalopathy, contraindications and warnings. However, it will be used investigationally in this trial as rifaximin is not FDA approved for the treatment of Alzheimer's Disease.

Rifaximin 550 milligrams (MG)

Duke University Medical Center

Trial of Rifaximin in Probable Alzheimer's Disease

Pilot, Single Center, Open, Trial of Rifaximin in Probable Alzheimer's Disease

Done at Baseline, 3 month and 5 month visits. ADAS-Cog is a widely used cognitive endpoint in AD clinical trials and changes on this scale, over time, are considered clinically meaningful. ADAS-11 range is 0-70 with higher scores indicating worse performance. Errors from 11 items are added to generate the total score.

Collected at every visit and follow-up phone visits. A rare side effect of Rifaximin is diarrhea caused by clostridium difficile. This is a very serious form of diarrhea that can be fatal if not treated. The investigators will be following the patients closely during treatment and for 2 months following treatment to see if the patient has any signs or symptoms of this diarrhea. If a patient does develop clostridium difficile diarrhea, they will be promptly treated.

Done at Baseline, 3 month and 5 month visits. When brain tissue is damaged, it releases substances (serum neuronal markers) into the blood, such as Neurofilament Light. The investigators will be looking for the amount of these serum neuronal markers to decrease after three months of Rifaximin treatment, indicating less brain tissue damage.

The investigators will be looking for changes in the amounts of the following pro-inflammatory markers:
Interleukin (IL) 1 beta, IL 2, IL 4, IL 5, IL 6, IL 8, IL 10, IL 13, Tumor necrosis factor - alpha

The study drug, Rifaximin, is an antibiotic. It changes the mixture of bacteria in the colon. The investigators will analyze the types of bacteria that are in the patient's colon. The microbiome variables the investigators will use standard FDR correction to examine nominal significance of change from baseline. The investigators will be assessing the Escherichia, shigella, pseudomonas, bacteroides, eubacterium and Faecalibacterium.

Assessed at every visit. The patients will be followed closely to see if they are tolerating the drug, Rifaximin. The of the number of side effects would indicate that the patient may not be tolerating the drug. Most of these side effects are minor and include headache, nausea, vomiting, tiredness. A potentially fatal side effect would be the development of clostridium difficile diarrhea. The investigators will be following the patients closely during treatment and for 2 months following treatment to see if the patient has any signs or symptoms of this diarrhea. If a patient does develop clostridium difficile diarrhea, they will be promptly treated.

Change from baseline global cognitive scores at month 3). Global cognitive performance will be assessed by a psychometrician using the (MMSE). It is a brief cognitive questionnaire with a maximum score of 30 points. MMSE range is 0-30 with lower scores indicating worse performance. The number of correct answers is added to generate the total score.

Safety will be measured through adverse events as reported by the subjects

Clinically significant deviations from the baseline on CBC will be considered an AE and clinically significant

Clinically significant deviations from baseline to month 3 in blood pressure.

Clinically significant deviations from baseline to month 3 in pulse.

Clinically significant deviations from the baseline on Chemistry values as defined as Creatine, blood urine nitrogen, electrolytes and sodium potassium chloride results will be considered an AE.

Clinically significant deviations from the baseline on LFT will be considered an AE.

Clinically significant deviations from the baseline on clinically significant and newly emergent C Difficile infection will be considered.

Duke University

Bausch Health Americas, Inc.

children aged 0-5 years who received general anesthesia and developed perioperative desaturation

children aged 0-5 years who received general anesthesia and did not developed perioperative desaturation

Low IQ

Disorder of Growth and Development

children aged 0-5 years old who receive general anesthesia and developed perioperative desaturation

perioperative desaturation

children aged 0-5 years who did not developed perioperative desaturation under general anesthesia

no perioperative desaturation

Prince of Songkla University

Growth and Intelligence Outcome in Children Who Developed Perioperative Desaturation

Possible Effect of Peri-operative Desaturation on Growth and Intelligence Outcome in Children Undergone General Anesthesia at a Tertiary Care Hospital in Southern Thailand

gamma aminobutyric acid/necrosis

Clarithromycin Mechanisms in Hypersomnia Syndromes

Trial of Rifaximin in Probable Alzheimer's Disease

Growth and Intelligence Outcome in Children Who Developed Perioperative Desaturation

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