Opioid Induced Pharyngeal and Esophageal DysfunctionPhase 4NCT01191645
Opioid Effects on Swallowing and Esophageal Sphincter Pressure
A Phase 4 study testing naloxone, remifentanil and Sodium Chloride in people with Opioid Induced Pharyngeal and Esophageal Dysfunction, run by Region Örebro County at 1 site in Sweden.
Trial summary
The purpose of this study is to determine whether a dopamine receptor antagonist metoclopramide can counteract opioid induced effects on esophageal motility and lower esophageal sphincter. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid Induced Pharyngeal and Esophageal Dysfunction
- What is being tested?
- naloxone, remifentanil and Sodium Chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteSweden
- Study dates
- Oct 2010to Nov 2010
- 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 history of cardiac, pulmonary or neurological disease
- Ongoing medication
- Allergies to or history of reaction to naloxone, remifentanil, fentanyl analogues or metoclopramide
- Pregnancy or breast feeding
- BMI > 30
- Previous participation in a medical clinical trial where opioid has been used or have during last 30 days participated in any other medicinal clinical trial or in a trial where follow-up in not completed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Can Opioid Induced Effects on Esophageal Motility and Lower Esophageal Sphincter be Counteracted by a Dopamine Receptor Antagonist?
The purpose of this study is to determine whether a dopamine receptor antagonist metoclopramide can counteract opioid induced effects on esophageal motility and lower esophageal sphincter. The aim of this study is also to evaluate if the opioid antagonist naloxone reduces the opioid induced pharyngeal and esophageal dysfunction.
Read the detailed description
Opioids induce pharyngeal and esophageal dysfunction and reduce the lower esophageal sphincter (LES) pressure, and thereby decreases the barrier pressure between the stomach and esophagus. This contributes to an increased risk of regurgitation and aspiration during anaesthesia induction and in the postoperative period, when the patient is treated with opioids for pain relief.
The effect of opioid antagonists on the opioid induced pharyngeal dysfunction and lower esophageal sphincter pressure are unknown. In a recently performed clinical trial we found that the peripheral opioid antagonist methylnaltrexone didn't have effect on the pharyngeal induced pharyngeal and esophageal dysfunction.This indicates that the negative opioid induced effects are not peripherally induced or mediated via peripheral opioid receptors.
In previously performed studies most of the volunteers reported swallowing problems when receiving infusion of the opioid remifentanil, we have also found that remifentanil abolished spontaneous esophageal motility.
The purpose of the study is to evaluate if opioid induced effects on the lower esophageal sphincter can be counteracted by a dopamine receptor antagonist, metoclopramide. It is previously known that dopamine, a catecholamine neurotransmitter, decreases the lower esophageal sphincter pressure and that a dopamine antagonist has the ability to increase the pressure.
Further in this study we want to evaluate if the opioid antagonist naloxone, which affects both peripheral and central opioid receptors, reduces the opioid induced pharyngeal and esophageal dysfunction.
A third aim of the study is to evaluate if the previously reported swallowing difficulties during infusion of opioid remifentanil are dose related, consequently does a higher concentration of opioids increase the swallowing difficulties.
The pharyngeal and esophageal motility/function can be registered in an easy and objective way with the high resolution manometry, ManoScan 360. ManoScan 360 is an equipment with 36 sensors at 1 cm spacing with 12 tip transducers at every sensor. The 36 closely spaced sensors automatically capture all relevant motor function from the pharynx to the stomach. The system collects reliable and consistent data records with improved diagnostic accuracy, and the data are analyzed using ManoView analyzes software. ManoScan 360 has a CE mark approval and has been used at Örebro University Hospital during the last three years.
- Being tested
- naloxone, remifentanil, Sodium Chloride, metoclopramide
- Keywords
- Lower esophageal sphincter pressure, Esophageal motility, Remifentanil, Metoclopramide, Naloxone, High resolution solid state manometry
- Medical subject headings
- Esophageal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
naloxoneDrug
Also called Naloxon, ACT-code: V03AB15
Injection fluid, solution 0,4 mg/kg Bolus infusion 6ug/kg at one occasion Continuous infusion 0,1 ug/kg/minute during 50 min
remifentanilDrug
Also called Ultiva, ATC-code: N01AH06
Powder for injection/ infusion fluid solution, 2 mg Infusion TCI 1ng/kg 10 min ( 0,05 ug/kg/min) Infusion TCI 2ng/kg 10 min ( 0.10 ug/kg/min) Infusion TCI 3ng/kg 20 min ( 0,15 ug/kg/min)
Sodium ChlorideDrug
Also called Natriumklorid, ACT-code: B05XA03
Infusion fluid, solution 9 mg/ml ( hydrogenic solution )
metoclopramideDrug
Also called Primperan
Injection fluid, solution 5 mg/mg Iv injection 0,2 mg/kg at one occasion
| Study group | Role | What they receive |
|---|---|---|
| Primperan | Experimental | Not described Receives: Drug: metoclopramide |
| Naloxon | Active comparator | Not described Receives: Drug: naloxone |
| Natriumklorid | Placebo comparator | Not described Receives: Drug: Sodium Chloride |
| Ultiva | Experimental | Not described Receives: Drug: remifentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lower esophageal sphincter pressure
Measured: 2 hours
Secondary outcomes (1)
Swallowing difficulties
The volunteers will be asked to do dry swallowing and assess the swallowing difficulty on the basis of following criteria: no difficulties, mild, moderate or severe difficulties.
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2010 (estimated)
- Study startOct 2010
- Primary completionNov 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid Induced Pharyngeal and Esophageal 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Region Örebro County
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Johanna Savilampi, Region Örebro County
- Investigators
- Magnus Wattwil, MD, Principal investigator, University Hospital Örebro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01191645
- Sponsor's protocol ID
- JS002
- Status last verified
- Jan 2012
- First submitted
- 30 Aug 2010
- Last updated
- 2 Feb 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can Opioid Induced Effects on Esophageal Motility and Lower Esophageal Sphincter be Counteracted by a Dopamine Receptor Antagonist?
- ClinicalTrials.gov ID
- NCT01191645
- Acronym / sponsor ID
- JS002
- Keywords
- Lower esophageal sphincter pressure, Esophageal motility, Remifentanil, Metoclopramide, Naloxone, High resolution solid state manometry
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Region Örebro CountyUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 31 Aug 2010 (estimated)
- 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 this study is to determine whether a dopamine receptor antagonist metoclopramide can counteract opioid induced effects on esophageal motility and lower esophageal sphincter. The aim of this study is also to evaluate if the opioid antagonist naloxone reduces the opioid induced pharyngeal and esophageal dysfunction.
Detailed description
Opioids induce pharyngeal and esophageal dysfunction and reduce the lower esophageal sphincter (LES) pressure, and thereby decreases the barrier pressure between the stomach and esophagus. This contributes to an increased risk of regurgitation and aspiration during anaesthesia induction and in the postoperative period, when the patient is treated with opioids for pain relief.
The effect of opioid antagonists on the opioid induced pharyngeal dysfunction and lower esophageal sphincter pressure are unknown. In a recently performed clinical trial we found that the peripheral opioid antagonist methylnaltrexone didn't have effect on the pharyngeal induced pharyngeal and esophageal dysfunction.This indicates that the negative opioid induced effects are not peripherally induced or mediated via peripheral opioid receptors.
In previously performed studies most of the volunteers reported swallowing problems when receiving infusion of the opioid remifentanil, we have also found that remifentanil abolished spontaneous esophageal motility.
The purpose of the study is to evaluate if opioid induced effects on the lower esophageal sphincter can be counteracted by a dopamine receptor antagonist, metoclopramide. It is previously known that dopamine, a catecholamine neurotransmitter, decreases the lower esophageal sphincter pressure and that a dopamine antagonist has the ability to increase the pressure.
Further in this study we want to evaluate if the opioid antagonist naloxone, which affects both peripheral and central opioid receptors, reduces the opioid induced pharyngeal and esophageal dysfunction.
A third aim of the study is to evaluate if the previously reported swallowing difficulties during infusion of opioid remifentanil are dose related, consequently does a higher concentration of opioids increase the swallowing difficulties.
The pharyngeal and esophageal motility/function can be registered in an easy and objective way with the high resolution manometry, ManoScan 360. ManoScan 360 is an equipment with 36 sensors at 1 cm spacing with 12 tip transducers at every sensor. The 36 closely spaced sensors automatically capture all relevant motor function from the pharynx to the stomach. The system collects reliable and consistent data records with improved diagnostic accuracy, and the data are analyzed using ManoView analyzes software. ManoScan 360 has a CE mark approval and has been used at Örebro University Hospital during the last three years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Primperan | Experimental | Drug: metoclopramide |
| Naloxon | Active comparator | Drug: naloxone |
| Natriumklorid | Placebo comparator | Drug: Sodium Chloride |
| Ultiva | Experimental | Drug: remifentanil |
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 (7 listed)
- Anamnesis of pharyngoesophageal dysfunction
- Known history of cardiac, pulmonary or neurological disease
- Ongoing medication
- Allergies to or history of reaction to naloxone, remifentanil, fentanyl analogues or metoclopramide
- 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 |
|---|---|---|
| naloxoneAlso: Naloxon, ACT-code: V03AB15Injection fluid, solution 0,4 mg/kg Bolus infusion 6ug/kg at one occasion Continuous infusion 0,1 ug/kg/minute during 50 min | Drug | Naloxon |
| remifentanilAlso: Ultiva, ATC-code: N01AH06Powder for injection/ infusion fluid solution, 2 mg Infusion TCI 1ng/kg 10 min ( 0,05 ug/kg/min) Infusion TCI 2ng/kg 10 min ( 0.10 ug/kg/min) Infusion TCI 3ng/kg 20 min ( 0,15 ug/kg/min) | Drug | Ultiva |
| Sodium ChlorideAlso: Natriumklorid, ACT-code: B05XA03Infusion fluid, solution 9 mg/ml ( hydrogenic solution ) | Drug | Natriumklorid |
| metoclopramideAlso: PrimperanInjection fluid, solution 5 mg/mg Iv injection 0,2 mg/kg at one occasion | Drug | Primperan |
Primary outcome
Lower esophageal sphincter pressure
Time frame: 2 hours
1 secondary outcome
Swallowing difficulties
Time frame: 2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2012.
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.
Magnus Wattwil, MD principal investigator
University Hospital 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 naloxone, remifentanil and Sodium Chloride in people with Opioid Induced Pharyngeal and Esophageal Dysfunction, 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 7 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 2 Feb 2012. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Lower esophageal sphincter pressure (time frame: 2 hours). 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 2 Feb 2012.