Pharyngeal DysfunctionPhase 4NCT03283020
Opioid-Induced Swallowing Dysfunction - The Impact of Bolus Volume
A Phase 4 study testing RemifentanilMNTX in people with Pharyngeal Dysfunction and Pharyngeal Swallowing, run by Region Örebro County at 1 site in Sweden.
Trial summary
The purpose of the study is to evaluate the impact of different bolus volumes and viscosity on remifentanil-induced swallowing dysfunction in healthy volunteers.Hence, whether swallowing tasks can be done safer during sedation by altering bolus volumes and viscosities will be revealed. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharyngeal Dysfunction, Pharyngeal Swallowing
- What is being tested?
- RemifentanilMNTX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteSweden
- Study dates
- 11 Nov 2017to 1 Apr 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- ≥ 18 - ≤ 40 year old healthy volunteers from both sexes.
- Have signed and dated Informed Consent.
- Willing and able to comply with the protocol for the duration of the trial.
Who cannot join
- Anamnesis of pharyngoesophageal dysfunction.
- Known or history of gastrointestinal, severe cardiac, pulmonary or neurological disease
- Ongoing medication that may affect upper gastrointestinal tract, larynx or lower airway.
- Allergies to or history of reaction to remifentanil, fentanyl analogues or dexmedetomidine.
- Pregnancy or breast feeding
- BMI > 30
- Smoking
- Previous participation in a medicinal clinical trial during the last year where an opioid has been used or have during the last 30 days participated in any other medicinal clinical trial or in a trial where follow-up is not completed.
Trial locations and contacts
1 site in 1 country.
Sweden1 site, 1 recruiting
- Recruiting
Department of Anaesthesiology and Intensive Care, Örebro University Hospital
Örebro, 70185
Johanna Savilampi, Phd, johanna.savilampi@regionorebrolan.se
Per Cajander, MD, per.cajander@regionorebrolan.se
About this study
Official title: Opioid-Induced Swallowing Dysfunction - The Impact of Bolus Volume: a Randomized, Double-Blind Study in Healthy Volunteers
The purpose of the study is to evaluate the impact of different bolus volumes and viscosity on remifentanil-induced swallowing dysfunction in healthy volunteers.Hence, whether swallowing tasks can be done safer during sedation by altering bolus volumes and viscosities will be revealed. Furthermore, the study will clarify underlying mechanisms (central vs. peripheral effects) of remifentanil-induced swallowing dysfunction. If methylnaltrexone reverses the remifentanil-induced effects on swallowing, this would suggest a dominant peripherally mediated mechanism.
Read the detailed description
Monitored anesthesia care (MAC) is commonly applied in modern perioperative care and means that minor surgical procedures are accomplished in awake patients using local anesthesia and light sedation. MAC has many advantages compared to general anesthesia; the recovery time after anesthesia is shorter and risk for postoperative nausea is lower to mention some. However, the patient is spontaneously breathing and the airway is not protected by an endotracheal tube which potentially increases risk of pulmonary aspiration. Pulmonary aspiration, that is inhalation of stomach and/or pharyngeal contents into the lungs, is a severe anesthesia-related complication and can in worst case lead to pneumonia and even death. Intact swallowing function is crucial in avoiding aspiration and how sedatives and analgesic agents used during MAC influence swallowing function is not fully understood.
Pharyngeal function during bolus swallowing is measured by combined high resolution impedance manometry (HRIM). The HRIM catheter is inserted through the nose in such a way that sensors straddle the entire pharynx and esophagus with the distal catheter tip in the stomach. Dynamic pressure changes and flow can be detected during swallowing and data registered by HRIM are analysed using purpose-designed software, AIM analysis (automated impedance manometry analysis). AIM analysis derives pressure flow variables which describe different physiological events like bolus timing and bolus distension in the pharynx and the esophagus during swallowing. A Swallow Risk Index value, quantifying risk of deglutitive aspiration, can also be defined.
The aim of the study is to evaluate impact of different bolus volumes on remifentanil-induced swallowing dysfunction in healthy volunteers. The study will clarify underlying mechanisms (central vs. peripheral effects) of remifentanil-induced swallowing dysfunction. Furthermore, whether swallowing tasks can be done safer during sedation by altering bolus volumes will be revealed. In addition to bolus volume, different bolus viscosities will be tested. It is shown that higher bolus viscosity diminishes misdirected swallows in dysphagic patients and higher bolus viscosity may possibly counteracts the swallowing dysfunction induced by remifentanil. Moreover, if MNTX reverses the remifentanil-induced effects on swallowing, then this would suggest a dominant peripherally mediated mechanism. Our aim is also to evaluate impact of remifentanil exposure on esophageal motility and impact of methylnaltrexone alone on swallowing function.
20 healthy volunteers will be studied on two different occasions approximately one week apart. In a randomized order volunteers will receive intravenous infusion of remifentanil and an intravenous injection of MNTX on one occasion, and placebo (normal saline) infusion and an intravenous injection of MNTX on the other occasion. Blood samples are obtained for plasma concentration determination of the study drug and sedation levels are assessed during study drug exposure.
- Conditions
- Pharyngeal Dysfunction, Pharyngeal Swallowing
- Being tested
- RemifentanilMNTX, PlaceboMNTX
- Keywords
- Remifentanil, Methylnaltrexone, Pharyngeal dysfunction, Anesthetic sedation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemifentanilMNTXDrug
Also called Methylnaltrexone, Remifentanil, Relistor, Ultiva
Remifentanil infusion TCI 3 ng/ml, Methylnaltrexone injection 0.3 mg/kg
PlaceboMNTXDrug
Also called Sodium Chloride 0.9%, Methylnaltrexone, Relistor
Placebo (NaCl 0.9%) TCI infusion, Methylnaltrexone injection 0.3 mg/kg
| Study group | Role | What they receive |
|---|---|---|
| RemifentanilMNTX | Active comparator | Volunteers are given an intravenous infusion with remifentanil, with an effect-site target concentration of 3 ng/ml via a target-controlled infusion (TCI) pump. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given. Receives: Drug: RemifentanilMNTX |
| PlaceboMNTX | Active comparator | Volunteers are given an intravenous infusion with saline 0,9%. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given. Receives: Drug: PlaceboMNTX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pressure Flow pharyngeal variables, 10 ml vs 20 ml bolus
Difference in pharyngeal pressure flow variables during remifentanil exposure between bolus volumes of 10 ml and 20 ml compared to placebo.
Measured: Up to 60 minutes
Secondary outcomes (7)
Pressure Flow pharyngeal variables, liquid vs semisolid bolus
Difference in pharyngeal pressure flow variables during remifentanil exposure between liquid and semisolid boluses compared to placebo
Measured: Up to 60 minutes
Pressure Flow pharyngeal variables, remifentanil before vs after methylnaltrexone
Difference in pharyngeal pressure flow variables during remifentanil exposure before and after methylnaltrexone administration compared to placebo.
Measured: Up to 60 minutes
Pressure Flow pharyngeal variables, placebo before vs after methylnaltrexone
Difference in pharyngeal pressure flow variables during placebo infusion before and after methylnaltrexone administration.
Measured: Up to 60 minutes
Pressure Flow esophageal motility variables, 10 ml vs 20 ml bolus
Difference in variables of esophageal motility between different bolus volumes during remifentanil exposure compared to placebo.
Measured: Up to 60 minutes
Pressure Flow esophageal motility variables, liquid vs semisolid bolus
Difference in variables of esophageal motility between liquid and semisolid boluses during remifentanil exposure compared to placebo.
Measured: Up to 60 minutes
Pressure Flow esophageal motility variables, remifentanil before vs after methylnaltrexone
Difference in variables of esophageal motility during remifentanil exposure before and after methylnaltrexone administration compared to placebo.
Measured: Up to 60 minutes
Pressure Flow esophageal motility variables, placebo before vs after methylnaltrexone
Difference in variables of esophageal motility during placebo infusion before and after methylnaltrexone administration.
Measured: Up to 60 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2017
- Study start11 Nov 2017
- Primary completion1 Apr 2018 (estimated)
- Study completion1 Apr 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pharyngeal DysfunctionStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Region Örebro County
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Johanna Savilampi, Region Örebro County
- Investigators
- Johanna Savilampi, MD, PhD, Principal investigator, University hospital in Örebro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03283020
- Sponsor's protocol ID
- JS006
- Status last verified
- Dec 2017
- First submitted
- 12 Sep 2017
- Last updated
- 12 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Opioid-Induced Swallowing Dysfunction - The Impact of Bolus Volume: a Randomized, Double-Blind Study in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03283020
- Acronym / sponsor ID
- JS006
- Conditions
- Pharyngeal Dysfunction, Pharyngeal Swallowing
- Keywords
- Remifentanil, Methylnaltrexone, Pharyngeal dysfunction, Anesthetic sedation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Region Örebro CountyUniversity, hospital or other
- Study start
- 11 Nov 2017 (actual)
- Primary completion
- 1 Apr 2018 (estimated)
- Study completion
- 1 Apr 2018 (estimated)
- First posted
- 14 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to evaluate the impact of different bolus volumes and viscosity on remifentanil-induced swallowing dysfunction in healthy volunteers.Hence, whether swallowing tasks can be done safer during sedation by altering bolus volumes and viscosities will be revealed. Furthermore, the study will clarify underlying mechanisms (central vs. peripheral effects) of remifentanil-induced swallowing dysfunction. If methylnaltrexone reverses the remifentanil-induced effects on swallowing, this would suggest a dominant peripherally mediated mechanism.
Detailed description
Monitored anesthesia care (MAC) is commonly applied in modern perioperative care and means that minor surgical procedures are accomplished in awake patients using local anesthesia and light sedation. MAC has many advantages compared to general anesthesia; the recovery time after anesthesia is shorter and risk for postoperative nausea is lower to mention some. However, the patient is spontaneously breathing and the airway is not protected by an endotracheal tube which potentially increases risk of pulmonary aspiration. Pulmonary aspiration, that is inhalation of stomach and/or pharyngeal contents into the lungs, is a severe anesthesia-related complication and can in worst case lead to pneumonia and even death. Intact swallowing function is crucial in avoiding aspiration and how sedatives and analgesic agents used during MAC influence swallowing function is not fully understood.
Pharyngeal function during bolus swallowing is measured by combined high resolution impedance manometry (HRIM). The HRIM catheter is inserted through the nose in such a way that sensors straddle the entire pharynx and esophagus with the distal catheter tip in the stomach. Dynamic pressure changes and flow can be detected during swallowing and data registered by HRIM are analysed using purpose-designed software, AIM analysis (automated impedance manometry analysis). AIM analysis derives pressure flow variables which describe different physiological events like bolus timing and bolus distension in the pharynx and the esophagus during swallowing. A Swallow Risk Index value, quantifying risk of deglutitive aspiration, can also be defined.
The aim of the study is to evaluate impact of different bolus volumes on remifentanil-induced swallowing dysfunction in healthy volunteers. The study will clarify underlying mechanisms (central vs. peripheral effects) of remifentanil-induced swallowing dysfunction. Furthermore, whether swallowing tasks can be done safer during sedation by altering bolus volumes will be revealed. In addition to bolus volume, different bolus viscosities will be tested. It is shown that higher bolus viscosity diminishes misdirected swallows in dysphagic patients and higher bolus viscosity may possibly counteracts the swallowing dysfunction induced by remifentanil. Moreover, if MNTX reverses the remifentanil-induced effects on swallowing, then this would suggest a dominant peripherally mediated mechanism. Our aim is also to evaluate impact of remifentanil exposure on esophageal motility and impact of methylnaltrexone alone on swallowing function.
20 healthy volunteers will be studied on two different occasions approximately one week apart. In a randomized order volunteers will receive intravenous infusion of remifentanil and an intravenous injection of MNTX on one occasion, and placebo (normal saline) infusion and an intravenous injection of MNTX on the other occasion. Blood samples are obtained for plasma concentration determination of the study drug and sedation levels are assessed during study drug exposure.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RemifentanilMNTX | Active comparator | Drug: RemifentanilMNTXVolunteers are given an intravenous infusion with remifentanil, with an effect-site target concentration of 3 ng/ml via a target-controlled infusion (TCI) pump. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given. |
| PlaceboMNTX | Active comparator | Drug: PlaceboMNTXVolunteers are given an intravenous infusion with saline 0,9%. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- ≥ 18 - ≤ 40 year old healthy volunteers from both sexes.
- Have signed and dated Informed Consent.
- Willing and able to comply with the protocol for the duration of the trial.
Key exclusion criteria (8 listed)
- Anamnesis of pharyngoesophageal dysfunction.
- Known or history of gastrointestinal, severe cardiac, pulmonary or neurological disease
- Ongoing medication that may affect upper gastrointestinal tract, larynx or lower airway.
- Allergies to or history of reaction to remifentanil, fentanyl analogues or dexmedetomidine.
- Pregnancy or breast feeding
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 |
|---|---|---|
| RemifentanilMNTXAlso: Methylnaltrexone, Remifentanil, Relistor, UltivaRemifentanil infusion TCI 3 ng/ml, Methylnaltrexone injection 0.3 mg/kg | Drug | RemifentanilMNTX |
| PlaceboMNTXAlso: Sodium Chloride 0.9%, Methylnaltrexone, RelistorPlacebo (NaCl 0.9%) TCI infusion, Methylnaltrexone injection 0.3 mg/kg | Drug | PlaceboMNTX |
Primary outcome
Pressure Flow pharyngeal variables, 10 ml vs 20 ml bolus
Time frame: Up to 60 minutes
Difference in pharyngeal pressure flow variables during remifentanil exposure between bolus volumes of 10 ml and 20 ml compared to placebo.
7 secondary outcomes
Pressure Flow pharyngeal variables, liquid vs semisolid bolus
Time frame: Up to 60 minutes
Pressure Flow pharyngeal variables, remifentanil before vs after methylnaltrexone
Time frame: Up to 60 minutes
Pressure Flow pharyngeal variables, placebo before vs after methylnaltrexone
Time frame: Up to 60 minutes
Pressure Flow esophageal motility variables, 10 ml vs 20 ml bolus
Time frame: Up to 60 minutes
Pressure Flow esophageal motility variables, liquid vs semisolid bolus
Time frame: Up to 60 minutes
Pressure Flow esophageal motility variables, remifentanil before vs after methylnaltrexone
Time frame: Up to 60 minutes
Pressure Flow esophageal motility variables, placebo before vs after methylnaltrexone
Time frame: Up to 60 minutes
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2017.
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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.
Johanna Savilampi, MD, PhD principal investigator
University hospital in Örebro
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 RemifentanilMNTX in people with Pharyngeal Dysfunction and Pharyngeal Swallowing, run by Region Örebro County at 1 site in Sweden.
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 3 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 12 Dec 2017. 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 Sweden. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Johanna Savilampi, MD, PhD (+46196020266, johanna.savilampi@regionorebrolan.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pressure Flow pharyngeal variables, 10 ml vs 20 ml bolus (time frame: Up to 60 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Dec 2017.