The Effect of S-ketamine on Pharmacokinetics of Morphine, Hydromorphone, and BuprenorphinePhase 1KetaMoHydBupNCT05571176
KetaMoHydBup: Pharmacokinetic Interaction of S-ketamine, Morphine, Hydromorphone and Buprenorphine
A Phase 1 study testing S-ketamine in people with The Effect of S-ketamine on Pharmacokinetics of Morphine, Hydromorphone, and Buprenorphine, run by Elina Brinck.
Trial summary
S-ketamine is often administered as a part of multimodal analgesia to reduce postoperative pain and postoperative opioid consumption. Current data indicates that ketamine may be useful for patients with prior use of opioids whereas the benefit for opioid-naive patients is less clear. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- The Effect of S-ketamine on Pharmacokinetics of Morphine, Hydromorphone, and Buprenorphine
- What is being tested?
- S-ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- Jan 2023to Dec 2023
- Phase
- Phase 1
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- written informed consent
- age 18-45 years
- healthy
- Normal values in the following laboratory assessments: Hb, P-ALAT, P-AFOS, P-GT, P-creatinine, P-K, P-Na, chemical sample for urine (U-KemSeul). Pregnancy test (P-hCG-tot) must be negative.
- Urine sample for detection of any illegal drugs must be negative (U-Huum-PS)
- Normal EKG
- Normal blood pressure
- No prior use of illicit drugs
Who cannot join
- Tendency/predisposition to illicit drug use, illicit drug use in history
- Abnormal EKG
- smoking
- use of oral contraceptives
- pregnancy, lactation
- participating in a less tha 3 months ago
Show all 9Show fewer
- Blood donation less than 3 months ago
- The subject's peripheral veins are hardly visible (predisposing difficulties in cannulation)
- weight less than 50 kg, body mass index (BMI) less than 18,5 or over 30
Trial locations and contacts
No sites are listed yet.
About this study
S-ketamine is often administered as a part of multimodal analgesia to reduce postoperative pain and postoperative opioid consumption. Current data indicates that ketamine may be useful for patients with prior use of opioids whereas the benefit for opioid-naive patients is less clear. However, different opioids have variable pharmacokinetic characteristics. Therefore, it is important to evaluate S-ketamine's effect on the pharmacokinetics of opioids.
Read the detailed description
S-ketamine is often used as a part of multimodal analgesia to reduce postoperative pain and opioid consumption, in part by mitigating opioid tolerance and opioid-induced hyperalgesia. However, there are mixed results concerning the effect of ketamine for this indication. Different opioids have various pharmacokinetic characteristics. Ketamine is known to inhibit the liver UGT2B7-enzyme, that is responsible for e.g., morphine metabolism. Therefore, it is important to investigate whether there is a clinically important pharmacokinetic interaction between S-ketamine and opioids metabolized via liver UGT2B7 enzyme. These opioids include morphpine, hydromorphone and buprenoprhine.
- Conditions
- The Effect of S-ketamine on Pharmacokinetics of Morphine, Hydromorphone, and Buprenorphine
- Being tested
- S-ketamine
- Keywords
- S-ketamine, hepatic UGT2B7 enzyme, pharmacokinetic interaction, morphine, hydromorphone, buprenorphine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S-ketamineDrug
S-ketamine infusion 0.29 mg/kg/h for 4 hours
| Study group | Role | What they receive |
|---|---|---|
| S-ketamine infusion | Experimental | 12 healthy volunteers, S-ketamine infusion 0.29 mg/kg/h for 4 hours Receives: Drug: S-ketamine |
| Placebo (NaCl 0.9%) infusion | Placebo comparator | 12 healthy volunteers, placebo (NaCl 0.9%) infusion for 4 hours Receives: Drug: S-ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration versus time curve (AUC) of morphine, hydromorphone and buprenorphine after intravenous S-ketamine infusion.
We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine and morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.
Measured: Time points for the measurements after the initiation of S-ketamine infusion: 0 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes and 210 minutes
Peak plasma concentrations (Cmax) of morphine, hydromorphone and buprenorphine after intravenous S-ketamine infusion
We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine, morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.
Measured: Time points for assessing peak plasma concentrations (Cmax) for morphine, hydromorphone and buprenorphine are the following: 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes, 210 minutes after the initiation of S-ketamine infusion.
Half-life time (t1/2) of morphine, hydromorphone and buprenorphine concentrations after intravenous S-ketamine infusion.
We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine, morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.
Measured: Time points for assessing half-life time of morphine, hydromorphone and buprenorphine are 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes and 210 minutes after initiation of S-ketamine infusion.
Secondary outcomes (5)
The effect of S-ketamine on brain-derived neurotrophic factor (BDNF) release
We measure BDNF plasma levels (ng/ml) during and after intravenous S-ketamine infusion .
Measured: Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion
The effect of S-ketamine on vascular endothelial growth factor (VEGF) release
We measure VEGF levels (ng/l) during and after intravenous S-ketamine infusion.
Measured: Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion.
The effect of S-ketamine infusion on prolactin release.
We measure prolactin levels (mU/l) during and after intravenous S-ketamine infusion.
Measured: Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion
The effect of S-ketamine infusion on cortisol release.
We measure cortisol levels (nmol/l) during and after intravenous S-ketamine infusion.
Measured: Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion
The effect of S-ketamine infusion on thrombocyte aggregation.
We evaluate the effect of intravenous S-ketamine infusion on thrombocyte aggregation by using Platelet Function Analyzer (PFA), a method that is based on the property of platelets to adhere upon shear stress conditions and aggregate in consequence of agonist presence in the system. We assess the clotting time. Unit of analysis is seconds (s).
Measured: At 2 hours after initiation of S-ketamine infusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2022
- Study startJan 2023 (estimated)
- Primary completionJun 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for The Effect of S-ketamine on Pharmacokinetics of Morphine, Hydromorphone, and BuprenorphineStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This is a cross-over study with two phases on 12 healthy volunteers. Study participants will be administered S-ketamine 0.29mg/kg/h intravenously or placebo (NaCl 0.9%) for 4 hours. 30 minutes after the initiation of the study drug infusion, each subject will be given single boluses of morphine 0.01mg/kg, hydromorphone 0.002mg/kg and buprenorphine 0.003mg/kg IV. We will analyze pharmacokinetic parameters (Cmax, tmax, AUC, t1/2) for morphine, hydromorphone, and buprenorphine. The aim of the study is to evaluate whether S-ketamine has a pharmacokinetic interaction with the opioids (morphine, hydromorphone, buprenorphine) known to be metabolized via liver UGT2B7 enzyme.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Elina Brinck
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Elina Brinck, Helsinki University Central Hospital
- Investigators
- Tuomas Lilius, MD, PhD, Principal investigator, University of Helsinki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05571176
- Sponsor's protocol ID
- EBrinck
- Other IDs
- 2021-006011-28
- Acronym
- KetaMoHydBup
- Status last verified
- Sep 2022
- First submitted
- 28 Sep 2022
- Last updated
- 7 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- KetaMoHydBup: Pharmacokinetic Interaction of S-ketamine, Morphine, Hydromorphone and Buprenorphine
- ClinicalTrials.gov ID
- NCT05571176
- Acronym / sponsor ID
- KetaMoHydBup / EBrinck
- Conditions
- The Effect of S-ketamine on Pharmacokinetics of Morphine, Hydromorphone, and Buprenorphine
- Keywords
- S-ketamine, hepatic UGT2B7 enzyme, pharmacokinetic interaction, morphine, hydromorphone, buprenorphine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Elina BrinckUniversity, hospital or other
- Study start
- Jan 2023 (estimated)
- Primary completion
- Jun 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 7 Oct 2022 (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.
S-ketamine is often administered as a part of multimodal analgesia to reduce postoperative pain and postoperative opioid consumption. Current data indicates that ketamine may be useful for patients with prior use of opioids whereas the benefit for opioid-naive patients is less clear. However, different opioids have variable pharmacokinetic characteristics. Therefore, it is important to evaluate S-ketamine's effect on the pharmacokinetics of opioids.
Detailed description
S-ketamine is often used as a part of multimodal analgesia to reduce postoperative pain and opioid consumption, in part by mitigating opioid tolerance and opioid-induced hyperalgesia. However, there are mixed results concerning the effect of ketamine for this indication. Different opioids have various pharmacokinetic characteristics. Ketamine is known to inhibit the liver UGT2B7-enzyme, that is responsible for e.g., morphine metabolism. Therefore, it is important to investigate whether there is a clinically important pharmacokinetic interaction between S-ketamine and opioids metabolized via liver UGT2B7 enzyme. These opioids include morphpine, hydromorphone and buprenoprhine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a cross-over study with two phases on 12 healthy volunteers. Study participants will be administered S-ketamine 0.29mg/kg/h intravenously or placebo (NaCl 0.9%) for 4 hours. 30 minutes after the initiation of the study drug infusion, each subject will be given single boluses of morphine 0.01mg/kg, hydromorphone 0.002mg/kg and buprenorphine 0.003mg/kg IV. We will analyze pharmacokinetic parameters (Cmax, tmax, AUC, t1/2) for morphine, hydromorphone, and buprenorphine. The aim of the study is to evaluate whether S-ketamine has a pharmacokinetic interaction with the opioids (morphine, hydromorphone, buprenorphine) known to be metabolized via liver UGT2B7 enzyme.
| Arm | Type | Receives |
|---|---|---|
| S-ketamine infusion | Experimental | Drug: S-ketamine12 healthy volunteers, S-ketamine infusion 0.29 mg/kg/h for 4 hours |
| Placebo (NaCl 0.9%) infusion | Placebo comparator | Drug: S-ketamine12 healthy volunteers, placebo (NaCl 0.9%) infusion for 4 hours |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- written informed consent
- age 18-45 years
- healthy
- Normal values in the following laboratory assessments: Hb, P-ALAT, P-AFOS, P-GT, P-creatinine, P-K, P-Na, chemical sample for urine (U-KemSeul). Pregnancy test (P-hCG-tot) must be negative.
- Urine sample for detection of any illegal drugs must be negative (U-Huum-PS)
Key exclusion criteria (9 listed)
- Tendency/predisposition to illicit drug use, illicit drug use in history
- Abnormal EKG
- smoking
- use of oral contraceptives
- pregnancy, lactation
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 |
|---|---|---|
| S-ketamineS-ketamine infusion 0.29 mg/kg/h for 4 hours | Drug | Placebo (NaCl 0.9%) infusion, S-ketamine infusion |
Primary outcome
Area under the plasma concentration versus time curve (AUC) of morphine, hydromorphone and buprenorphine after intravenous S-ketamine infusion.
Time frame: Time points for the measurements after the initiation of S-ketamine infusion: 0 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes and 210 minutes
We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine and morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.
Peak plasma concentrations (Cmax) of morphine, hydromorphone and buprenorphine after intravenous S-ketamine infusion
Time frame: Time points for assessing peak plasma concentrations (Cmax) for morphine, hydromorphone and buprenorphine are the following: 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes, 210 minutes after the initiation of S-ketamine infusion.
We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine, morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.
Half-life time (t1/2) of morphine, hydromorphone and buprenorphine concentrations after intravenous S-ketamine infusion.
Time frame: Time points for assessing half-life time of morphine, hydromorphone and buprenorphine are 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes and 210 minutes after initiation of S-ketamine infusion.
We aim to investigate whether there is a clinically significant pharmacokinetic interaction between S-ketamine, morphine, S-ketamine and hydromorphone and S-ketamine and buprenorphine.
5 secondary outcomes
The effect of S-ketamine on brain-derived neurotrophic factor (BDNF) release
Time frame: Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion
The effect of S-ketamine on vascular endothelial growth factor (VEGF) release
Time frame: Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion.
The effect of S-ketamine infusion on prolactin release.
Time frame: Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion
The effect of S-ketamine infusion on cortisol release.
Time frame: Time points for assessments: 30 minutes, 120 minutes, 240 minutes, 360 minutes, 480 minutes and at Day1 after the intiation of S-ketamine infusion
The effect of S-ketamine infusion on thrombocyte aggregation.
Time frame: At 2 hours after initiation of S-ketamine infusion.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2022.
- Individual participant dataSharing planned: No
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.
Tuomas Lilius, MD, PhD principal investigator
University of Helsinki
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing S-ketamine in people with The Effect of S-ketamine on Pharmacokinetics of Morphine, Hydromorphone, and Buprenorphine, run by Elina Brinck.
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 8 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: status not confirmed, as of the sponsor's last update on 7 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Elina CV Brinck, MD, PhD (+358504286267, elina.brinck@hus.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the plasma concentration versus time curve (AUC) of morphine, hydromorphone and buprenorphine after intravenous S-ketamine infusion. (time frame: Time points for the measurements after the initiation of S-ketamine infusion: 0 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes and 210 minutes). The study lists 3 primary outcomes in all. 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 7 Oct 2022.