Pharmacological Activation of HMN for OSA

Study Overview
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Brief Summary
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Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. OSA patients show a marked reduction in upper airway (UA) dilator muscle activity at sleep onset and this phenomenon leads to increased collapsibility of UA compared to normal subjects. In this protocol the investigators will test the effect of LTM1201L, LTM1201LN, LTM1201LB, LTM1201LD administered before sleep on OSA phenotype traits and OSA severity during sleep.

Official Title
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Pharmacological Activation of Hypoglossal Motor Nucleus for Obstructive Sleep Apnea

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: Placebo oral capsule
* Drug: LTM1201L
* Drug: LTM1201LN
* Drug: LTM1201LB
* Drug: LTM1201LD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AHI > 10 events/h during NREM supine sleep Exclusion Criteria: Any medical condition other than well controlled hypertension and mild diabetes. Any medication known to influence breathing, sleep/arousal, or muscle physiology. Claustrophobia. Inability to sleep supine. Allergy to any of the medications tested in the protocol. History of kidney stones, hypercalcemia, primary hyperparathyroidism, sarcoidosis, hypervitaminosis D. Individuals with underlying cardiac disease, such as arrhythmias. Individuals taking psychiatric medications, such as an MAO-I, SSRI or SNRI, or any of the studied medications for medical care. For women: Pregnancy. Pulmonary hypertension Severe OSA with a mean SaO2 lower than 88%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo capsule 1 time before bedtime | Drug: Placebo oral capsule<br>* Placebo capsule before sleep<br>|
| Active Comparator: LTM1201L<br>LTM1201L capsule 1 time before bedtime | Drug: LTM1201L<br>* LTM1201L capsule before sleep<br>|
| Active Comparator: LTM1201LN<br>LTM1201LN capsule 1 time before bedtime | Drug: LTM1201LN<br>* LTM1201LN capsule before sleep<br>|
| Active Comparator: LTM1201LB<br>LTM1201LB capsule 1 time before bedtime | Drug: LTM1201LB<br>* LTM1201LB capsule before sleep<br>|
| Active Comparator: LTM1201LD<br>LTM1201LD capsule 1 time before bedtime | Drug: LTM1201LD<br>* LTM1201LD capsule before sleep<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apnea Hypopnea Index (AHI, Average Number of Events for Every Hour of Sleep) | Based on previous studies the investigators anticipate that active comparators will reduce AHI more effectively in subjects with moderate sleep apnea and low-to-moderate collapsibility (Vpassive >50% of eupneic values). Higher AHI indicates more severe OSA, usually ranging between 10 to 110 events/hour. | 1 night | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Collapsibility of the Upper Airway: VActive (L/Min) | VActive: ventilation when ventilatory drive is high and pharyngeal dilator muscles are relatively active. | 1 night |