Cardiometabolic Risk Effects of Short-term Cessation of Neurostimulation Therapy (CRESCENT)

Cardiometabolic Risk Effects of Short-term Cessation of Effective Neurostimulation Therapy in OSA

Hypoglossal nerve stimulation (HGNS) is an implantable therapy that treats obstructive sleep apnea.

The study will evaluate the effect of this treatment on cardiovascular and metabolism-related measures to see if it affects patients' risk of medical problems associated with obstructive sleep apnea (OSA).

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea; Obstructive Sleep Apnea of Adult
• Intervention / Treatment: Device: No HGNS therapy (HGNS-off)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Otolaryngology Research Group; Phone Number: 646-317-3252; Email: otosleepresearch@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Jesus Lopez; Phone Number: 646-317-3252; Email: otosleepresearch@cumc.columbia.edu
      • Principal Investigator: Yi Cai, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• English-speaking adults (18+ years) who have met surgical efficacy criteria with HGNS, as defined by at least a 50% reduction in apnea-hypopnea index (AHI) to <20 (with hypopneas defined by 4% oxyhemoglobin desaturations)
• Have been using HGNS therapy for at least 3 months and used HGNS for >20 hours/week during the past 4 weeks
• Were not using any OSA therapy for at least one month prior to HGNS activation or have had a one-month period of untreated OSA after HGNS activation

Exclusion Criteria:

• Chronic use of opiate medications, illicit drugs, or alcohol dependency
• Women who are pregnant or planning to become pregnant
• Shift workers, heavy machinery operators, or commercial drivers
• History of severe excessive daytime sleepiness (Epworth Sleepiness Scale score >16 at time of screening or prior to HGNS), motor vehicle accidents or near-miss incidents due to drowsy driving within the year prior to enrollment
• Significant cardiopulmonary (such as home oxygen requirement), liver, renal, or oncologic disease; neurodegenerative disease; active or recent history of an eating disorder (within the last 5 years)
• Inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: No HGNS therapy (HGNS-off); HGNS therapy will be turned off by the participant for this arm of the study. This arm will mimic the participant's untreated OSA statement before they had HGNS therapy activated.	Device: No HGNS therapy (HGNS-off); Prior to enrollment in this study, participants will have been utilizing HGNS at a therapeutic voltage setting confirmed via overnight sleep study. As part of the trial, they will undergo a study arm that involves turning off HGNS therapy (HGNS-off) for between 2-4 weeks.
No Intervention: Therapeutic HGNS (HGNS-on); Prior to enrollment in this study, participants will have been implanted with and stabilized on HGNS therapy. As part of clinical care, a therapeutic voltage setting will have been confirmed via overnight sleep study. This arm of the study maintains the participants on the HGNS therapy at the therapeutic voltage they have been using. This is a representation of the patient's baseline status.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free living energy expenditure	The investigators will measure energy expenditure using the doubly labeled water (DLW) technique and actigraphy.	Data will be obtained in the last 2 weeks of each study phase (HGNS-on or HGNS-off)
Hypoxic burden	The investigators will measure hypoxic burden based on the home sleep testing obtained during the study.	Data will be obtained in the last 2 weeks of each study phase (HGNS-on or HGNS-off).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin resistance	Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) will be derived from fasting glucose and insulin	These measures will be taken at the end of each study phase (duration of 2-4 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leptin levels	Serum leptin will be measured using a double-antibody radioimmunoassay (RIA).	At the end of each study phase (duration of 2-4 weeks)
Adiponectin levels	Adiponectin levels will be analyzed using RIA.	At the end of each study phase (duration of 2-4 weeks)
Ghrelin levels	Total ghrelin will be assessed using RIA.	At the end of each study phase (duration of 2-4 weeks)
Glucagon-like peptide-1 (GLP-1) levels	GLP-1 will be measured by RIA after plasma extraction with 95% ethanol.	At the end of each study phase (duration of 2-4 weeks)
E-selectin levels	E-selectin will be measured as an inflammatory marker.	At the end of each study phase (duration of 2-4 weeks)
Vascular endothelial growth factor-A (VEGF-A) levels	VEGF-A will be measured as an inflammatory marker.	At the end of each study phase (duration of 2-4 weeks)
Apnea-Hypopnea Index (AHI)	The participants will undergo home sleep testing, which will report an AHI value.	These measures will be taken at the end of each study phase (duration of 2-4 weeks)
Height in meters	Participants' height will be measured without shoes.	This measure will be taken at each study visit (duration of 1-4 weeks)
Weight in kilograms	Participants' weight will be measured after a urine void	This measure will be taken at every study visit (duration 1-4 weeks)
Waist circumference in centimeters	Participants' waist circumference will be measured	This measure will be taken at every study visit (duration 1-4 weeks)
Sleep duration (minutes)	The investigators will measure sleep duration in minutes based on actigraphy.	Data will be obtained in the last 2 weeks of each study phase (HGNS-on or HGNS-off)

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: American Heart Association; American Academy of Sleep Medicine; Triological Society

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: October 1, 2024
• First Submitted That Met QC Criteria: December 2, 2024
• First Posted (Actual): December 6, 2024

Study Record Updates

• Last Update Posted (Actual): July 10, 2025
• Last Update Submitted That Met QC Criteria: July 5, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: hypoglossal nerve stimulation; inspire
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: AAAU9827

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Participant PHI protection

Drug and device information, study documents

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