Combination Pharmacological Interventions for Multiple Mechanisms of Obstructive Sleep Apnea

• Status: Recruiting
• Trial end date: 2021-09-15
• Target enrollment: 0
• Participant gender: All

Summary

Currently, there is no pharmacological intervention for OSA that targets multiple pathophysiological deficits in combination. Here the investigators study the effect on sleep apnea severity of combinations of pharmacological agents that stimulate the pharyngeal muscles, stabilize ventilatory control, and increase the arousal threshold.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Collaborator: Apnimed

Criteria

Inclusion criteria:

• Ages 18 - 79 years

• Suspected or diagnosed OSA

Exclusion criteria:

• Any uncontrolled medical condition

• Current use of the medications under investigation

• Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).

• Current use of hypnotic medications (trazodone, eszopiclone, benzodiazepines).

• Current use of SNRIs/SSRIs or anticholinergic medications.

• Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.

• Respiratory disorders other than sleep disordered breathing:

chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.

• Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.

• Contraindications for SAS0421a and SAS0421b, including:

• hypersensitivity to SAS0421a and SAS0421b (angioedema or urticaria)

• pheochromocytoma

• use of monoamine oxidase inhibitors

• benign prostatic hypertrophy, urinary retention

• untreated narrow angle glaucoma

• bipolar disorder, mania, psychosis

• history of major depressive disorder (age<24).

• history of attempted suicide or suicidal ideation within one year prior to screening

• clinically significant constipation, gastric retention

• pre-existing seizure disorders

• clinically-significant kidney disorders (eGFR<60 ml/min/1.73m2)

• clinically-significant liver disorders

• clinically-significant cardiovascular conditions

• severe hypertension (SBP>180 mmHg or DBP>110 mmHg measured at baseline)

• cardiomyopathy (LVEF<50%) or heart failure

• advanced atherosclerosis

• history of cerebrovascular events

• history of cardiac arrhythmias e.g., atrial fibrillation, QT prolongation

• other serious cardiac conditions that would raise the consequences of an increase in blood pressure or heart rate

• myasthenia gravis

• pregnancy/breast-feeding

• Additional contraindications for SAS0421c, including:

• Use more than 500 mg/day of Aspirin

• Allergies to this drug class

• Adrenocortical insufficiency

• Low sodium or potassium

• hyperchloremic acidosis

• Claustrophobia

• Pregnancy or nursing