DAW2020 on OSA Endotypic Traits

Official title

Effect of DAW2020 on Endotypic Traits in OSA

Overview

Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. Some OSA patients with low arousal threshold wake up prematurely during an obstructive event and do not have time for spontaneous upper airway (UA) dilator muscle recruitment. As a consequence they are exposed to apnea and hypopnea cycling. In this protocol the investigators will test the effect of DAW2020 administered before sleep on OSA phenotype traits and OSA severity during sleep.

Detailed description

Two overnight sleep studies will be performed: a drug night and a placebo night. The patient will breath spontaneously (without CPAP) for both nights. On the study nights, subjects will present to the laboratory in the evening and be instrumented with a full polysomnigraphy for monitoring sleep, physiological variables (endotypes), and respiratory events. A history and physical examination will be performed on each night prior to beginning the study, as will a urine pregnancy test in premenopausal women. DAW2020 34 mg will be given 4 hours before lights out. Subjects will sleep at least 50% of the night in the supine position. At least four hours of sleep with high quality signal acquisition will be required for a study to be judged adequate. After the first overnight study is completed, there will be a one-week washout period prior to crossing over to the other treatment.

Interventions

• Drug Placebo oral capsule
  Placebo before sleep
• Drug DAW2020 oral capsule
  DAW2020 34 mg 4 h before sleep, single night administration

Primary outcome measures

• Effects of DAW2020 on arousal threshold (%eupnea) [Time frame: 1 night]

Eligibility criteria

Inclusion criteria

• Moderate-to-severe OSA (AHI ≥ 15 events/hr)

Exclusion criteria

• All participants will be healthy and without major organ system disease that would preclude undergoing the physiological measurements.
• Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, acetazolamide, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
• Use of SNRIs/SSRIs.
• Conditions likely to affect OSA physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.
• Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea:
• Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.
• Hypersensitivity to the study drug (angioedema or urticaria)
• Contraindications to DAW2020
• Use of medications that lengthen QTc interval
• Hypokaliemia, hypomagnesemia, uncontrolled thyroid disease
• Severe claustrophobia.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Brigham and Women's Hospital — Boston

Publications

• Messineo L, Gell L, Calianese N, Sofer T, Vena D, Azarbarzin A, Labarca G, Taranto-Montemurro L, Yang HC, Wang TY, Kim M, Smith H, White D, Sands S, Wellman A. Effect of Pimavanserin on the Respiratory Arousal Threshold from Sleep: A Randomized Trial. Ann Am Thorac Soc. 2022 Dec;19(12):2062-2069. doi: 10.1513/AnnalsATS.202205-419OC. PMID 35947827

Identifiers

NCT: NCT04538755 · 2020p002760-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗