PainPhase 4NCT00921765
Reversal of Ketamine Pharmacodynamic Effects With Naloxone
A Phase 4 study testing Saline, Saline + Ketamine and Naloxone + Ketamine in people with Pain, run by Ullevaal University Hospital at 1 site in Norway.
Trial summary
The purpose of this study is to determine whether the analgetic and other effects effect of ketamine are partly mediated through opioid receptors Read more about this study
- Who is it for?
- Ages 18 to 30 years, women only
- Conditions the study is for
- Pain
- What is being tested?
- Saline, Saline + Ketamine and Naloxone + Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteNorway
- Study dates
- Dec 2009to Dec 2017
- 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 30 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Females of norwegian Caucasian origin who needs surgical removal of impacted third molars
Who cannot join
- Anamnestic information regarding psychiatric diagnosis regarding mother/father or brother/sister Concommitant medication other than oral contraceptives Hypersensitivity towards NSAID/opioids/study drugs Females with suspected or confirmed pregnancy Lactating females Surgery lasting more than 60 minutes
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Naloxone Block of Low-dose (Analgetic Dose) Ketamine
The purpose of this study is to determine whether the analgetic and other effects effect of ketamine are partly mediated through opioid receptors
Read the detailed description
Ketamine er et dissociative anaesthetic closely related with phencyclidine (PCP). Phencyclidine is a non-competitive NMDA-antagonist, and it is assumed that the pharmacodynamic mechanism of action for ketamine is the same. Receptor binding studies shows that ketamine has affinity to many receptor types, including opioid mu and kappa receptors. Ketamine has only about 25 times lower affinity for kappa receptors than for the NMDA-receptor complex. Naloxone is a specific antagonist for opioid receptors and block both mu og kappa receptors. A dose of naloxone 10 times larger than required to block mu receptors is required to block kappa receptors. Experiments with naloxone suggest that ketamine is not a mu agonist, but experiments with sufficient large naloxone doses to block kappa receptors have not been carried out in humans.
- Conditions
- Pain
- Being tested
- Saline, Saline + Ketamine, Naloxone + Placebo, Naloxone + Ketamine
- Keywords
- Pain, Naloxone, Ketamine, Third Molar, Surgery
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalineDrug
Also called Physiological saline 0.9%
Saline single bolus dose followed by saline single bolus dose iv
Saline + KetamineDrug
Also called Physiological saline 0.9%, Ketamine, ATC code: N01A X03
Single bolus dose of saline followed by ketamine 0.2 mg/kg bw
Naloxone + PlaceboDrug
Also called Naloxone, ATC code: V03A B15, Physiological saline 0.9%
Single bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of saline
Naloxone + KetamineDrug
Also called Naloxone, ATC code: V03A B15, Ketamine, ATC code: N01A X03
Single bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of ketamine 0.2 mg/kg bw
| Study group | Role | What they receive |
|---|---|---|
| Placebo + Placebo | Placebo comparator | Saline single bolus dose iv + saline single bolus dose iv Receives: Drug: Saline |
| Placebo + Ketamine | Active comparator | Saline single bolus dose followed by single bolus dose of ketamine 0.2 mg/kg bw Receives: Drug: Saline + Ketamine |
| Naloxone + Placebo | Active comparator | Single bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of saline Receives: Drug: Naloxone + Placebo |
| Naloxone + Ketamine | Active comparator | Single bolus dose of ketamine 0.2 mg/kg bw followed by single bolus dose of ketamine 0.2 mg/kg bw Receives: Drug: Naloxone + Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain intensity (0-10 Numerical Rating Scale)
Measured: 30 minutes
Secondary outcomes (2)
Subjective measurement of psychotomimetic effects
Measured: 30 minutes
Adverse effects
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2009 (estimated)
- Study startDec 2009
- Primary completionDec 2017
- Study completionDec 2017
Why it stopped: Problems with patient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for PainStudies 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
- Parallel groups
- Model description
- Parallell Group design should be used when final dose had been found
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ullevaal University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oslo
- Responsible party
- Principal investigator, Lasse Ansgar Skoglund, Oslo University Hospital
- Investigators
- Olav Hustveit, MD, PhD, Study director, University of OsloElena Landari, DDS, Principal investigator, University of Oslo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00921765
- Sponsor's protocol ID
- DOK-018
- Status last verified
- Apr 2018
- First submitted
- 15 Jun 2009
- Last updated
- 5 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Gear RW, Miaskowski C, Gordon NC, Paul SM, Heller PH, Levine JD. Kappa-opioids produce significantly greater analgesia in women than in men. Nat Med. 1996 Nov;2(11):1248-50. doi: 10.1038/nm1196-1248.
PubMed 8898754Hustveit O, Maurset A, Oye I. Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors. Pharmacol Toxicol. 1995 Dec;77(6):355-9. doi: 10.1111/j.1600-0773.1995.tb01041.x.
PubMed 8835358Mathisen LC, Skjelbred P, Skoglund LA, Oye I. Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain. Pain. 1995 May;61(2):215-220. doi: 10.1016/0304-3959(94)00170-J.
PubMed 7659431Oye I, Paulsen O, Maurset A. Effects of ketamine on sensory perception: evidence for a role of N-methyl-D-aspartate receptors. J Pharmacol Exp Ther. 1992 Mar;260(3):1209-13.
PubMed 1312163
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Naloxone Block of Low-dose (Analgetic Dose) Ketamine
- ClinicalTrials.gov ID
- NCT00921765
- Acronym / sponsor ID
- DOK-018
- Conditions
- Pain
- Keywords
- Pain, Naloxone, Ketamine, Third Molar, Surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Problems with patient recruitment
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Ullevaal University HospitalUniversity, hospital or other
- Collaborators
- University of Oslo
- Study start
- Dec 2009
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 16 Jun 2009 (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 the analgetic and other effects effect of ketamine are partly mediated through opioid receptors
Detailed description
Ketamine er et dissociative anaesthetic closely related with phencyclidine (PCP). Phencyclidine is a non-competitive NMDA-antagonist, and it is assumed that the pharmacodynamic mechanism of action for ketamine is the same. Receptor binding studies shows that ketamine has affinity to many receptor types, including opioid mu and kappa receptors. Ketamine has only about 25 times lower affinity for kappa receptors than for the NMDA-receptor complex. Naloxone is a specific antagonist for opioid receptors and block both mu og kappa receptors. A dose of naloxone 10 times larger than required to block mu receptors is required to block kappa receptors. Experiments with naloxone suggest that ketamine is not a mu agonist, but experiments with sufficient large naloxone doses to block kappa receptors have not been carried out in humans.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Parallell Group design should be used when final dose had been found
| Arm | Type | Receives |
|---|---|---|
| Placebo + Placebo | Placebo comparator | Drug: SalineSaline single bolus dose iv + saline single bolus dose iv |
| Placebo + Ketamine | Active comparator | Drug: Saline + KetamineSaline single bolus dose followed by single bolus dose of ketamine 0.2 mg/kg bw |
| Naloxone + Placebo | Active comparator | Drug: Naloxone + PlaceboSingle bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of saline |
| Naloxone + Ketamine | Active comparator | Drug: Naloxone + KetamineSingle bolus dose of ketamine 0.2 mg/kg bw followed by single bolus dose of ketamine 0.2 mg/kg bw |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Females of norwegian Caucasian origin who needs surgical removal of impacted third molars
Key exclusion criteria (1 listed)
- Anamnestic information regarding psychiatric diagnosis regarding mother/father or brother/sister Concommitant medication other than oral contraceptives Hypersensitivity towards NSAID/opioids/study drugs Females with suspected or confirmed pregnancy Lactating females Surgery lasting more than 60 minutes
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 |
|---|---|---|
| SalineAlso: Physiological saline 0.9%Saline single bolus dose followed by saline single bolus dose iv | Drug | Placebo + Placebo |
| Saline + KetamineAlso: Physiological saline 0.9%, Ketamine, ATC code: N01A X03Single bolus dose of saline followed by ketamine 0.2 mg/kg bw | Drug | Placebo + Ketamine |
| Naloxone + PlaceboAlso: Naloxone, ATC code: V03A B15, Physiological saline 0.9%Single bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of saline | Drug | Naloxone + Placebo |
| Naloxone + KetamineAlso: Naloxone, ATC code: V03A B15, Ketamine, ATC code: N01A X03Single bolus dose of naloxone 0.2 mg/kg bw followed by single bolus dose of ketamine 0.2 mg/kg bw | Drug | Naloxone + Ketamine |
Primary outcome
Pain intensity (0-10 Numerical Rating Scale)
Time frame: 30 minutes
2 secondary outcomes
Subjective measurement of psychotomimetic effects
Time frame: 30 minutes
Adverse effects
Time frame: 30 minutes
Results and safety
The study was stopped early (reason given: Problems with patient recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2018.
- Background: PubMed 8898754Gear RW, Miaskowski C, Gordon NC, Paul SM, Heller PH, Levine JD. Kappa-opioids produce significantly greater analgesia in women than in men. Nat Med. 1996 Nov;2(11):1248-50. doi: 10.1038/nm1196-1248.
- Background: PubMed 8835358Hustveit O, Maurset A, Oye I. Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors. Pharmacol Toxicol. 1995 Dec;77(6):355-9. doi: 10.1111/j.1600-0773.1995.tb01041.x.
- Background: PubMed 7659431Mathisen LC, Skjelbred P, Skoglund LA, Oye I. Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain. Pain. 1995 May;61(2):215-220. doi: 10.1016/0304-3959(94)00170-J.
- Background: PubMed 1312163Oye I, Paulsen O, Maurset A. Effects of ketamine on sensory perception: evidence for a role of N-methyl-D-aspartate receptors. J Pharmacol Exp Ther. 1992 Mar;260(3):1209-13.
- 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.
Olav Hustveit, MD, PhD study director
University of Oslo
Elena Landari, DDS principal investigator
University of Oslo
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 Saline, Saline + Ketamine and Naloxone + Ketamine in people with Pain, run by Ullevaal University Hospital at 1 site in Norway.
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 1 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: stopped early, as of the sponsor's last update on 5 Apr 2018. 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 Norway. 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 was stopped early (reason given: Problems with patient recruitment). Results are not available in the source record.
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?
Pain intensity (0-10 Numerical Rating Scale) (time frame: 30 minutes). 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 NCT00921765, which also lists 4 linked publications.
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 5 Apr 2018.