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Opioid Induced Respiratory DepressionPhase 1OXISNCT05730062

Influence of Oxycodone on Individuals Taking an SSRI

A Phase 1 study testing Oxycodone Hydrochloride in people with Opioid Induced Respiratory Depression and Depressive Disorder, run by Leiden University Medical Center.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study will determine whether selective serotonin reuptake inhibitors (SSRI) exacerbate opioid induced respiratory depression in patients initiating treatment for underlying conditions such as depression or an anxiety disorder. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Oxycodone Hydrochloride
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
55 participants
Where
No sites listed yet
Study dates
15 Mar 2023to 15 Apr 2025
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed the informed consent form (ICF) and able to comply with the study requirements and restrictions listed therein;
  • Male and female subjects, age 18 to 75 years, inclusive;
  • Women of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have a negative serum pregnancy test prior to enrolment and must agree to use a medically acceptable means of contraception from screening through at least 1 month after the last dose of study drug;
  • Body Mass Index (BMI) 18 to 35 kg/m2, inclusive;
  • Stable as defined by the Investigator, based on a medical evaluation that includes the subject's medical and surgical history, physical examination, vital signs;
  • Using sertraline (minimal dose 50 mg), paroxetine minimal dose 20 mg), citalopram (minimal dose 20 mg) or escitalopram (minimal dose 10 mg).

Who cannot join

  • Currently meet the criteria for diagnosis of moderate or severe substance use disorder according to the DSM-5 criteria on any substances other than caffeine, or nicotine;
  • Any active medical condition, organ disease or concurrent medication or treatment that may either compromise subject safety or interfere with study endpoints;
  • Consume, on average, >27 units/week of alcohol in men and >20 units/week of alcohol in women (1 unit = 1 glass (250 mL) beer, 125 mL glass of wine or 25 mL of 40% spirit);
  • Currently receiving medication-assisted treatment for the treatment of opioid-use disorder;
  • Require on-going prescription or over-the-counter medications that are clinically relevant CYP P450 3A4 or CYP P450 2C8 inducers or inhibitors (e.g., rifampicin, azole antifungals [e.g., ketoconazole], macrolide antibiotics [e.g., erythromycin]);
  • Significant traumatic injury, major surgery, or open biopsy within the prior 4 weeks of informed consent;
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  • History of substance use disorder;
  • History of suicidal ideation within 30 days prior to informed consent or history of a suicide attempt in the 6 months prior to informed consent;
  • Measured systolic blood pressure greater than 160 or less than 95 mmHg or diastolic pressure greater than 95 mmHg at screening;
  • History or presence of allergic response to study medication;
  • Treatment with another investigational drug within 3 months prior to dosing or having participated in more than 4 investigational drug studies within 1 year prior to screening;
  • Site staff or subjects affiliated with, or a family member of, site staff directly involved in the study.
  • Current use of any opioid.
  • Opioid use less than 4 weeks prior to dosing with oxycodone in the current study.

Trial locations and contacts

No sites are listed yet.

Rutger van der Schrier, MD contact

+31 (0)71 5299893

r.m.van_der_schrier@lumc.nl

About this study

This study will determine whether selective serotonin reuptake inhibitors (SSRI) exacerbate opioid induced respiratory depression in patients initiating treatment for underlying conditions such as depression or an anxiety disorder. Next to paroxetine which has been evaluated in a previous study in healthy volunteers sertraline, citalopram and escitalopram will be evaluated with regards to its influence on opioid induced respiratory depression.

Read the detailed description

Primary Objective:

To determine the effect of low-dose (10 mg) oxycodone versus placebo in individuals that use paroxetine on ventilation at an extrapolated end-tidal carbon dioxide concentration of 55 mmHg at 1 week (4-10 days) of SSRI treatment.

Secondary objectives:

To determine the effect of low-dose (10 mg) oxycodone versus placebo in individuals that either use sertraline, citalopram or escitalopram on ventilation at an extrapolated end-tidal carbon dioxide concentration of 55 mmHg at 1 week (4-10 days) of SSRI treatment.

To determine the effect of low dose (10 mg) oxycodone versus placebo in individuals that either use paroxetine, sertraline, citalopram or escitalopram on ventilation at an extrapolated end-tidal carbon dioxide concentration of 55 mmHg following at 1 month (25- 45 days) following initiation of SSRI treatment.

To determine whether the effects of SSRI on opioid induced respiratory depression alter during the course of treatment.

To determine the effect of low-dose oxycodone versus placebo in individuals that use and SSRI on pupil diameter.

To determine the effect of paroxetine on the pharmacokinetics of oxycodone.

Study design:

The design of the study is double-blind, placebo-controlled and cross over.

two groups will be studied: Time 1: individuals that use an SSRI for 1 week (day 4-10 after initiation of treatment); Time 2: (the same) individuals that use an SSRI for 1 month (day 25-45 after initiation of treatment); Subjects from Time 1 may transition to time 2 (preferably).

This is a crossover study. Subjects will be randomized (placebo vs oxycodone) with at least 2days in-between study days.

Subjects will be asked to take their antidepressant on t = 0 h, and will then dose the oxycodone on t = 2 h. Primary endpoint is ventilation measured at an extrapolated end-tidal PCO2 of 55 mmHg (VE55) at t = 4 h.

Prior to any antidepressant intake (t = 0) and at 1 h intervals following drug intake, the ventilatory response to hypercapnia will be measured for 6 hours. If VE55 is below 20% of baseline a further 1 or 2 measurements will be obtained

In between respiratory measurements, pupil diameter will be measured the using a handheld pupilometer. Additionally, subjects will be queried the at 1 h intervals for sedation,lightheadedness, nausea/vomiting using 11-point Likert scale from 0 (no effect) to 10 (max. possible effect).

In all subjects, a blood sample will be draw to determine the state of the CYP 2C8/3A4/2D6 gene to determine the metabolic state of the antidepressant among the subjects and relate this as covariate to our results. Additionally, 10 venous blood samples will be drawn for pharmacokinetic oxycodon analysis by Ardena (Assen). Blood will be drawn for a venipuncture in the arm or via an access line in the cubital vein. Blood sampling will be at t = 0 (blank), t = 15 min, 30 min, t = 45 min, t = 60 min, t = 120 min, t = 180 min, t = 240 min en t = 300 min.

SSRIs: the following SSRIs are planned to be studied :

  • Paroxetine, dose at least 20 mg (Primary endpoint)
  • Citalopram , dose at least 20 mg
  • Escilatopram, dose at least 10 mg,
  • Sertraline, dose at least 50 mg
Being tested
Oxycodone Hydrochloride, Placebo
Medical subject headings
Depressive Disorder, Anxiety Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oxycodone HydrochlorideDrug

    Also called oxynorm

    Oxycodone 10 mg IR

  • PlaceboDrug

    placebo comparator

Study groups in NCT05730062
Study groupRoleWhat they receive
SSRI 1 week following initiation oxycodoneExperimentalPatients will be included day 4-10 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and will be administered oxycodone 10 mg IR
Receives: Drug: Oxycodone Hydrochloride
SSRI 1 week following initiation placeboPlacebo comparatorPatients will be included day 25-45 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and and will be administered placebo comparator
Receives: Drug: Placebo
SSRI 1 month following initiation oxycodoneExperimentalPatients will be included day 25-45 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and and will be administered oxycodone 10 mg IR.
Receives: Drug: Oxycodone Hydrochloride
SSRI 1 month following initiation placeboPlacebo comparatorPatients will be included day 25-45 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and and will be administered placebo comparator.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ve55 Paroxetine 1 week

    After one week of starting Paroxetine, extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be measured, followed by oxycodone or placebo ingestion. The extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be assessed two hours after oxycodone/placebo ingestion. The change from the baseline will be determined.

    Measured: two hours following ingestion of the Paroxetine either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.

Secondary outcomes (5)
  1. Ve55 Sertraline, Citalopram, Escitalopram 1 week

    After one week of starting Sertraline or Citalopram or Escitalopram, extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be measured, followed by oxycodone or placebo ingestion. The extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be assessed two hours after oxycodone/placebo ingestion. The change from the baseline will be determined.

    Measured: two hours following ingestion of the Sertraline or Citalopram or Escitalopram either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.

  2. Ve55 Paroxetine, Sertraline, Citalopram, Escitalopram at 1 month

    After one month of starting Paroxetine, Sertraline or Citalopram or Escitalopram, extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be measured, followed by oxycodone or placebo ingestion. The extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be assessed two hours after oxycodone/placebo ingestion. The change from the baseline will be determined.

    Measured: two hours following ingestion of the Sertraline or Citalopram or Escitalopram either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.

  3. Ve55 over course Treatment

    After one month of starting Paroxetine, Sertraline or Citalopram or Escitalopram, extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be measured, followed by oxycodone or placebo ingestion. The extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be assessed two hours after oxycodone/placebo ingestion. The change from the baseline will be determined and will be compared to the results from 1 week following the initiation of treatment of the mentioned SSRIs

    Measured: two hours following ingestion of the Sertraline or Citalopram or Escitalopram either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.

  4. Pupillometry

    Pupil diameter will determined at regular intervals to determine the effect of low dose oxycodone vs placebo in patients that use an SSRIs, during all visits.

    Measured: Will be determined from pupillometry at t= 0,30,60,90,120,150,180,210,240,270,300 minutes

  5. Plasma concentration oxycodone

    Determine the effect of paroxetine on the pharmacokinetics of oxycodone, samples will be obtained during all visits.

    Measured: Will be determined from blood samples drawn at t= 0,15,30,45,60,120,180,240,300 minutes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2023
  2. Study start15 Mar 2023 (estimated)
  3. Primary completion15 Jan 2025 (estimated)
  4. Study completion15 Apr 2025 (estimated)

Resources

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
Basic science
Allocation
Randomised
Intervention model
Crossover
Model description
This is a placebo controlled (oxycodone vs placebo) crossover study in patients initiating one of the following SSRIs (Paroxetine, Sertraline, Citalopram, Escitalopram)
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
55 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05730062
Sponsor's protocol ID
P22.052
Acronym
OXIS
Status last verified
Feb 2023
First submitted
12 Jan 2023
Last updated
15 Feb 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Florian J, van der Schrier R, Gershuny V, Davis MC, Wang C, Han X, Burkhart K, Prentice K, Shah A, Racz R, Patel V, Matta M, Ismaiel OA, Weaver J, Boughner R, Ford K, Rouse R, Stone M, Sanabria C, Dahan A, Strauss DG. Effect of Paroxetine or Quetiapine Combined With Oxycodone vs Oxycodone Alone on Ventilation During Hypercapnia: A Randomized Clinical Trial. JAMA. 2022 Oct 11;328(14):1405-1414. doi: 10.1001/jama.2022.17735.

    PubMed 36219407
  • Cohen R, Finn H, Steen SN. Effect of diazepam and meperidine, alone and in combination, on respiratory response to carbon dioxide. Anesth Analg. 1969 May-Jun;48(3):353-5. No abstract available.

    PubMed 5815096
  • Geddes DM, Rudolf M, Saunders KB. Effect of nitrazepam and flurazepam on the ventilatory response to carbon dioxide. Thorax. 1976 Oct;31(5):548-51. doi: 10.1136/thx.31.5.548.

    PubMed 11571
  • Olsson M, Annerbrink K, Bengtsson F, Hedner J, Eriksson E. Paroxetine influences respiration in rats: implications for the treatment of panic disorder. Eur Neuropsychopharmacol. 2004 Jan;14(1):29-37. doi: 10.1016/s0924-977x(03)00044-0.

    PubMed 14659984
  • van der Schrier R, Roozekrans M, Olofsen E, Aarts L, van Velzen M, de Jong M, Dahan A, Niesters M. Influence of Ethanol on Oxycodone-induced Respiratory Depression: A Dose-escalating Study in Young and Elderly Individuals. Anesthesiology. 2017 Mar;126(3):534-542. doi: 10.1097/ALN.0000000000001505.

    PubMed 28170358
  • Xu L, Krishna A, Stewart S, Shea K, Racz R, Weaver JL, Volpe DA, Pilli NR, Narayanasamy S, Florian J, Patel V, Matta MK, Stone MB, Zhu H, Davis MC, Strauss DG, Rouse R. Effects of sedative psychotropic drugs combined with oxycodone on respiratory depression in the rat. Clin Transl Sci. 2021 Nov;14(6):2208-2219. doi: 10.1111/cts.13080. Epub 2021 Jun 16.

    PubMed 34080766
  • Yunusa I, Gagne JJ, Yoshida K, Bykov K. Risk of Opioid Overdose Associated With Concomitant Use of Oxycodone and Selective Serotonin Reuptake Inhibitors. JAMA Netw Open. 2022 Feb 1;5(2):e220194. doi: 10.1001/jamanetworkopen.2022.0194.

    PubMed 35201310

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Oxycodone Hydrochloride in people with Opioid Induced Respiratory Depression and Depressive Disorder, run by Leiden University Medical Center.

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 6 inclusion and 14 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 15 Feb 2023. 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 Rutger van der Schrier, MD (+31 (0)71 5299893, r.m.van_der_schrier@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ve55 Paroxetine 1 week (time frame: two hours following ingestion of the Paroxetine either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.). 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 NCT05730062, which also lists 7 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 15 Feb 2023.

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