Pharmacological Activation of HMN for OSA (OSA12)

Pharmacological Activation of Hypoglossal Motor Nucleus for Obstructive Sleep Apnea

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.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Placebo oral capsule; Drug: LTM1201L; Drug: LTM1201LN; Drug: LTM1201LB; Drug: LTM1201LD

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Sleep Disorders Research Program Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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%

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo capsule 1 time before bedtime	Drug: Placebo oral capsule; Placebo capsule before sleep
Active Comparator: LTM1201L; LTM1201L capsule 1 time before bedtime	Drug: LTM1201L; LTM1201L capsule before sleep
Active Comparator: LTM1201LN; LTM1201LN capsule 1 time before bedtime	Drug: LTM1201LN; LTM1201LN capsule before sleep
Active Comparator: LTM1201LB; LTM1201LB capsule 1 time before bedtime	Drug: LTM1201LB; LTM1201LB capsule before sleep
Active Comparator: LTM1201LD; LTM1201LD capsule 1 time before bedtime	Drug: LTM1201LD; LTM1201LD capsule before sleep

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2018
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: August 17, 2018
• First Posted (Actual): August 21, 2018

Study Record Updates

• Last Update Posted (Actual): February 24, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
• Other Study ID Numbers: 2018P001201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No