Sleep-disordered BreathingPhase 4NCT04720547
Sleep and Breathing in the General Population - Chemical Stimuli
A Phase 4 study testing Zolpidem and No Treatment in people with Sleep-disordered Breathing, run by Wayne State University at 1 site in United States.
Trial summary
Central sleep apnea (CSA) is a common condition and its treatment remains elusive. The focus of this proposal is to identify the role of the physiologic path involving cortical arousals in CSA by decreasing arousal frequency using the pharmacological agent zolpidem. Read more about this study
- Who is it for?
- Ages 18 to 89 yearsHealthy volunteers can take part
- Conditions the study is for
- Sleep-disordered Breathing
- What is being tested?
- Zolpidem and No Treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jul 2018to 29 Feb 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women Veterans with central sleep apnea, defined as Apnea Hypopnea Index (AHI)>15/hour with CAHI>5/hour, will be included in the experiments.
Who cannot join
- less than 18 years old
- pregnant or breastfeeding female
- have severe respiratory disease that require to be on oxygen
- recent health event that may affect the ability to participate in the study,
- Body Mass Index (BMI) is >40 kg/m2
- significant insomnia
Show all 9Show fewer
- mental instability
- recent health event that may affect sleep
- if at any time the principal investigator (PI) identifies that a certain drug is not suitable, or are unable to use the device that is used to treat sleep apnea, will be not be allowed to participate in the study
Trial locations and contacts
1 site in 1 country.
United States1 site
John D. Dingell VA Medical Center
Detroit, Michigan, 48201
About this study
Official title: Sleep and Breathing in Health and Disease (Part 2A - Chemical Stimuli, Sleep and Breathing in the General Population)
Central sleep apnea (CSA) is a common condition and its treatment remains elusive. The focus of this proposal is to identify the role of the physiologic path involving cortical arousals in CSA by decreasing arousal frequency using the pharmacological agent zolpidem. The goal is to identify the acute effects of administering zolpidem on sleep and respiratory outcomes, and subsequently, its effect on the severity of CSA and propensity to develop CSA. This study will shed light on the mechanisms underlying CSA that involve cortical arousals and will guide future therapeutic interventions for CSA.
Read the detailed description
The literature suggests that zolpidem may be effective in the treatment of central sleep apnea (CSA). However, evidence regarding the efficacy of zolpidem and the underlying mechanisms involved in its effect on CSA are not well-studied. Furthermore, respiratory-related arousals are hypothesized to contribute CSA symptoms and severity. The aim of the study is to determine the effect of decreasing respiratory-related arousals on the propensity to develop central apnea. The investigators hypothesize that administration of the nonbenzodiazepine hypnotic zolpidem will decrease the frequency of respiratory-related arousals, lower the central apnea-hypopnea index, and widen the CO2 reserve during sleep in patients with CSA compared to no treatment. Participants will complete a night study on a low dose of zolpidem and another night study without zolpidem in a crossover manner. The order of night studies is randomized. The results will help unveil the role of arousals in CSA and the acute effect of zolpidem on CSA severity and the propensity to CSA.
- Conditions
- Sleep-disordered Breathing
- Being tested
- Zolpidem, No Treatment
- Keywords
- Sleep-disordered Breathing, central sleep apnea
- Medical subject headings
- Sleep Apnea Syndromes, Sleep Apnea, Central
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZolpidemDrug
Also called Ambien
A nonbenzodiazepine hypnotic
No TreatmentOther
The Control condition in which participants do not receive medication.
| Study group | Role | What they receive |
|---|---|---|
| Zolpidem, then No Treatment | Experimental | Participants will be administered zolpidem for the first night study, and No Treatment during the second night study. Receives: Drug: Zolpidem; Other: No Treatment |
| No Treatment, then Zolpidem | Experimental | Participants will be administered zolpidem for the second night study, and No Treatment during the first night study. Receives: Drug: Zolpidem; Other: No Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Central Apnea-hypopnea Index
The number of central apneas and hypopneas per hour of sleep was obtained from polysomnography studies.
Measured: one night
Respiratory Arousal Index
A measure of the frequency of respiratory-related arousals during sleep
Measured: one night
Secondary outcomes (4)
CO2 Reserve
CO2 reserve is the requisite change to induce central apnea is referred to as the CO2 reserve, which can be positive or negative. CO2 reserve is defined as the difference between the eupneic end-tidal CO2 pressure and the end-tidal CO2 pressure induced by the ventilation protocol that is sufficient to trigger a central apnea as defined by the American Academy of Sleep Medicine.
Measured: one night
Controller Gain
Controller gain is a ventilatory response to changes in end-tidal PCO2. Controller gain was calculated by dividing the difference in minute ventilation between the post-mechanical ventilation induced by the ventilation protocol and steady-state respiration by the difference in the end-tidal CO2 pressure between the mechanical ventilation and steady-state respiration.
Measured: one night
Stead-State Plant Gain (mmHg
Plant gain is a blood gas response to a change in ventilation. This measure represents the effectiveness of the "plant" in eliminating CO2. Steady-state plant gain was calculated from the ratio of end-tidal CO2 to minute ventilation during stable respiration.
Measured: one night
Respiratory Arousal Threshold
The nadir pressure in the upper airway (supra-glottic pressure) prior to the occurrence of an arousal
Measured: one night
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2021
- Study start3 Jul 2018
- Primary completion29 Feb 2020
- Study completion29 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sleep-disordered BreathingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- After an initial assessment to determine eligibility, participant complete two in-lab night studies in a randomized manner including one night with the administration of zolpidem and another without zolpidem.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wayne State University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, M Safwan Badr, Wayne State University
- Investigators
- M Safwan Badr, MD, MBA, Principal investigator, John D. Dingell VA Medical Center, Detroit, MI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04720547
- Sponsor's protocol ID
- 1203010749
- Other IDs
- 5R01HL130552-05
- Status last verified
- Dec 2023
- First submitted
- 20 Jan 2021
- Last updated
- 6 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ahmad B, Sankari A, Eshraghi M, Aldwaikat A, Yarandi H, Zeineddine S, Salloum A, Badr MS. Effect of Zolpidem on nocturnal arousals and susceptibility to central sleep apnea. Sleep Breath. 2023 Mar;27(1):173-180. doi: 10.1007/s11325-022-02593-3. Epub 2022 Mar 14.
PubMed 35286569
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sleep and Breathing in Health and Disease (Part 2A - Chemical Stimuli, Sleep and Breathing in the General Population)
- ClinicalTrials.gov ID
- NCT04720547
- Acronym / sponsor ID
- 1203010749
- Conditions
- Sleep-disordered Breathing
- Keywords
- Sleep-disordered Breathing, central sleep apnea
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Wayne State UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 3 Jul 2018 (actual)
- Primary completion
- 29 Feb 2020 (actual)
- Study completion
- 29 Feb 2020 (actual)
- First posted
- 22 Jan 2021 (actual)
- Results
- Posted 28 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Central sleep apnea (CSA) is a common condition and its treatment remains elusive. The focus of this proposal is to identify the role of the physiologic path involving cortical arousals in CSA by decreasing arousal frequency using the pharmacological agent zolpidem. The goal is to identify the acute effects of administering zolpidem on sleep and respiratory outcomes, and subsequently, its effect on the severity of CSA and propensity to develop CSA. This study will shed light on the mechanisms underlying CSA that involve cortical arousals and will guide future therapeutic interventions for CSA.
Detailed description
The literature suggests that zolpidem may be effective in the treatment of central sleep apnea (CSA). However, evidence regarding the efficacy of zolpidem and the underlying mechanisms involved in its effect on CSA are not well-studied. Furthermore, respiratory-related arousals are hypothesized to contribute CSA symptoms and severity. The aim of the study is to determine the effect of decreasing respiratory-related arousals on the propensity to develop central apnea. The investigators hypothesize that administration of the nonbenzodiazepine hypnotic zolpidem will decrease the frequency of respiratory-related arousals, lower the central apnea-hypopnea index, and widen the CO2 reserve during sleep in patients with CSA compared to no treatment. Participants will complete a night study on a low dose of zolpidem and another night study without zolpidem in a crossover manner. The order of night studies is randomized. The results will help unveil the role of arousals in CSA and the acute effect of zolpidem on CSA severity and the propensity to CSA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- After an initial assessment to determine eligibility, participant complete two in-lab night studies in a randomized manner including one night with the administration of zolpidem and another without zolpidem.
| Arm | Type | Receives |
|---|---|---|
| Zolpidem, then No Treatment | Experimental | Drug: Zolpidem, Other: No TreatmentParticipants will be administered zolpidem for the first night study, and No Treatment during the second night study. |
| No Treatment, then Zolpidem | Experimental | Drug: Zolpidem, Other: No TreatmentParticipants will be administered zolpidem for the second night study, and No Treatment during the first night study. |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Men and women Veterans with central sleep apnea, defined as Apnea Hypopnea Index (AHI)>15/hour with CAHI>5/hour, will be included in the experiments.
Key exclusion criteria (9 listed)
- less than 18 years old
- pregnant or breastfeeding female
- have severe respiratory disease that require to be on oxygen
- recent health event that may affect the ability to participate in the study,
- Body Mass Index (BMI) is >40 kg/m2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZolpidemAlso: AmbienA nonbenzodiazepine hypnotic | Drug | No Treatment, then Zolpidem, Zolpidem, then No Treatment |
| No TreatmentThe Control condition in which participants do not receive medication. | Other | No Treatment, then Zolpidem, Zolpidem, then No Treatment |
Primary outcome
The Central Apnea-hypopnea Index
Time frame: one night
The number of central apneas and hypopneas per hour of sleep was obtained from polysomnography studies.
Respiratory Arousal Index
Time frame: one night
A measure of the frequency of respiratory-related arousals during sleep
4 secondary outcomes
CO2 Reserve
Time frame: one night
Controller Gain
Time frame: one night
Stead-State Plant Gain (mmHg
Time frame: one night
Respiratory Arousal Threshold
Time frame: one night
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35286569Ahmad B, Sankari A, Eshraghi M, Aldwaikat A, Yarandi H, Zeineddine S, Salloum A, Badr MS. Effect of Zolpidem on nocturnal arousals and susceptibility to central sleep apnea. Sleep Breath. 2023 Mar;27(1):173-180. doi: 10.1007/s11325-022-02593-3. Epub 2022 Mar 14.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
M Safwan Badr, MD, MBA principal investigator
John D. Dingell VA Medical Center, Detroit, MI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Zolpidem and No Treatment in people with Sleep-disordered Breathing, run by Wayne State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Central Apnea-hypopnea Index (time frame: one night). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04720547, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2023.