Opioid AbusePhase 1/2NCT00499746
The Discriminative Effects of Tramadol in Humans
A Phase 1/2 study testing tramadol, Hydromorphone and Methylphenidate in people with Opioid Abuse and Opioid Addiction, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
Trial summary
This research is part of a set of studies whose purpose is to test whether tramadol can be used for the treatment of opioid addiction. Tramadol is already available in the United States as a pain medicine marketed as Ultram. Read more about this study
- Who is it for?
- Ages 21 months to 55 years
- Conditions the study is for
- Opioid Abuse, Opioid Addiction, Stimulant Abuse
- What is being tested?
- tramadol, Hydromorphone and Methylphenidate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Aug 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 months to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Study subjects are male and female non-dependent opioid users with active stimulant use.
- Between the ages of 21-55
- In good physical health
- Without significant psychiatric illness besides their drug use.
- Females are required to provide a negative pregnancy test prior to study participation.
Who cannot join
- Subjects are excluded if they have evidence of significant medical (e.g., insulin dependent diabetes mellitus) or psychiatric (e.g., schizophrenia) illness.
- Subjects with a history of seizures will be excluded.
- Persons with current history of significant alcohol or sedative/hypnotic drug use will be excluded from study participation.
- Applicants seeking treatment for their substance abuse will not be admitted to the study, and will be provided information about treatment services available.
Trial locations and contacts
1 site in 1 country.
United States1 site
Behavioral Pharmacology Research Unit
Baltimore, Maryland, 21224
About this study
Official title: Medications Development for Drug Abuse Disorders
This research is part of a set of studies whose purpose is to test whether tramadol can be used for the treatment of opioid addiction. Tramadol is already available in the United States as a pain medicine marketed as Ultram. It has effects similar to morphine, and it may also have effects similar to other drugs like stimulants. The doses of tramadol used in this study are higher than those generally used for the treatment of pain. To be in this study a participant must be a user of opioids (drugs like heroin) and stimulants (drugs like cocaine), but cannot be addicted to either. The person must be between 21-55 years old, and generally healthy. Up to 12 people will take part in this study.
Read the detailed description
This is a human laboratory study that tests the effects of tramadol as a step in the possible development of this medication as a new treatment for opioid dependence. Tramadol is a mild/moderate mu agonist opioid currently marketed as an analgesic that has a unique profile of effects. One of the primary metabolites of tramadol, mono-O-demethyltramadol (referred to as M1) exerts opioid agonist effects at the mu receptor. In addition, tramadol and M1 produce reuptake blockade of monoamines, and this latter effect may positively influence its analgesic efficacy, in addition to influencing the subjective effects produced by tramadol. Preclinical evidence suggests that tramadol's effects on monoamine reuptake may have antidepressant qualities as well. Given tramadol's diverse pharmacodynamic profile, a systematic characterization of its subjective effects in opioid-experienced subjects would provide valuable information regarding its abuse liability, and its potential utility as a treatment for opioid dependence.
The characterization of an opioid medication's profile can be accomplished through a variety of experimental procedures. One useful procedure for assessing the profile of an opioid is a drug discrimination procedure. In this methodology, subjects are first trained to discriminate reference drugs such as placebo and an opioid agonist, and then administered doses of a novel compound to determine how like (or unlike) it is to the reference training conditions. Our laboratory has a long history of using this drug discrimination methodology to study and to characterize opioids with varying opioid receptor activity profiles. Studies have generally included either two or three training conditions in humans. Using this technique in volunteers, studies have characterized the profile of a number of opioids including (for example) butorphanol, nalbuphine, pentazocine, and buprenorphine.
While most of these studies testing the effects of mixed agonist-antagonist opioids have used an opioid agonist and placebo as the training conditions, tramadol's profile of effects suggests that there may be a non-opioid component of action at serotonin and norepinephrine sites that will be useful to distinguish. In particular, it is of interest to determine the extent to which tramadol is identified as being like a prototypic mu agonist opioid, whether it is substantially identified as being like a non-opioid compound, and if this non-opioid component is related to enhancement of monoamine effects. In order to provide a meaningful non-opioid contrast training condition, this study will compare different doses of tramadol to training conditions of placebo, a mu agonist opioid, and a prototypic stimulant.
Overall, this evaluation will provide a greater understanding of the subjective effect profile of tramadol in comparison to a prototypic mu opioid and a prototypic stimulant. If tramadol is to be useful in the treatment of opioid dependence, a thorough assessment of its subjective effects in experienced opioid and stimulant abusers is warranted.
- Conditions
- Opioid Abuse, Opioid Addiction, Stimulant Abuse, Stimulant Addiction
- Being tested
- tramadol, placebo, Hydromorphone, Methylphenidate
- Keywords
- drug discrimination, opioid pharmacology, behavioral pharmacology, human research
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tramadolDrug
Also called Ultram
oral dose, once per day
placeboDrug
Also called sugar pill
oral dose, once per day
HydromorphoneDrug
Also called Dilaudid
oral dose, once per day
MethylphenidateDrug
Also called stimulant
oral dose, once per day
| Study group | Role | What they receive |
|---|---|---|
| Tramadol | Active comparator | oral dose, once per day Receives: Drug: tramadol |
| Placebo | Placebo comparator | oral dose, once per day Receives: Drug: placebo |
| hydromorphone | Active comparator | oral dose, once per day Receives: Drug: Hydromorphone |
| methylphenidate | Active comparator | oral dose, once per day Receives: Drug: Methylphenidate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acquisition of Discrimination Assessed by Accuracy of the Discrimination Test
The acquisition of discrimination was to test whether volunteers could identify each training drug condition by the correct letter code. Results are the percentage of correct responses with a range of 0% to 100%.
Measured: 1 day
Discrimination Effects Assessed by Operant Responses
Volunteers emitted operant responses on computer keys that corresponded to the training letter, on a fixed interval 1 second schedule for 8.5 minutes. The range is from 0 to 500 operant responses.
Measured: 1 day
Discrimination Effects Assessed by Point Distribution
In point distribution, volunteers distributed 50 points among three training drug letters depending on how certain they were of the identity of the administrated drug. Maximum total is 50 points.
Measured: 1day
Discrimination Effects Assessed by Discrete Choice
During discrete choice, volunteers were given three choices (placebo, hydromorphone, methylphenidate) and were asked to choose which of the training drugs they thought they received. The outcome measure illustrates the percentage of participants who chose either placebo, hydromorphone, or methylphenidate during each drug condition (i.e., Placebo, Hydromorphone 8 mg, Tramadol 50 mg, etc.), ranging from 0-100.
The outcome measure represents the percentage of participants who chose either placebo, opioid agonist, or stimulant across each drug condition.
Measured: 1 day
Secondary outcomes (4)
Physiologic Effects Assessed by the Pharmacological Class Questionnaire
During the peak (assessed at 120 min) of each drug administration, participants were asked to complete the pharmacological class questionnaire. The pharmacological class questionnaire had volunteers indicate which drug class was most similar to the drug condition they received. Ten drug classes were listed with descriptive labels and examples of each: placebo, opiates (or opioid agonist), phenothiazines, barbiturates, antidepressants, opiate antagonists, hallucinogens, benzodiazepines, stimulants, and other. Of these choices, participants chose 3: placebo, opioid agonist, and stimulant.
The outcome measure represents the percentage of participants who chose either placebo, opioid agonist, or stimulant across each drug condition.
Measured: Measure at 120 min after drug administration
Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter
Change in pupil diameter (mm) at peak (120 min) compared to baseline measure of pupil diameter
Measured: Measure at 120 min after drug administration
Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS)
The Visual Analog Scale (VAS) measures subjective ratings of opioid agonist effects. The scale on this measure ranges from 0 being "Not at all" to 100 being "Extremely". On this scale, higher scores indicate a stronger drug effect. The outcome measure illustrates a difference from peak (120 min) to baseline measure on VAS.
Measured: Measure at 120 min after drug administration
Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS)
The Visual Analog Scale (VAS) measures subjective ratings of stimulant effects. The scale on this measure ranges from 0 being "Not at all" to 100 being "Extremely". On this scale, higher scores indicate a stronger drug effect. The outcome measure illustrates a difference from peak (120 min) to baseline measure.
Measured: Measure at 120 min after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2007 (estimated)
- Study startNov 2007
- Primary completionApr 2010
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid AbuseStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Eric Strain, MD, Johns Hopkins University
- Investigators
- Eric C Strain, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00499746
- Sponsor's protocol ID
- NIDA-18125-3
- Other IDs
- R01DA018125, DPMCDA
- Status last verified
- Sep 2017
- First submitted
- 9 Jul 2007
- Last updated
- 17 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Duke AN, Bigelow GE, Lanier RK, Strain EC. Discriminative stimulus effects of tramadol in humans. J Pharmacol Exp Ther. 2011 Jul;338(1):255-62. doi: 10.1124/jpet.111.181131. Epub 2011 Apr 5.
PubMed 21467190
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Medications Development for Drug Abuse Disorders
- ClinicalTrials.gov ID
- NCT00499746
- Acronym / sponsor ID
- NIDA-18125-3
- Conditions
- Opioid Abuse, Opioid Addiction, Stimulant Abuse, Stimulant Addiction
- Keywords
- drug discrimination, opioid pharmacology, behavioral pharmacology, human research
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Study start
- Nov 2007
- Primary completion
- Apr 2010 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 11 Jul 2007 (estimated)
- Results
- Posted 17 Oct 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research is part of a set of studies whose purpose is to test whether tramadol can be used for the treatment of opioid addiction. Tramadol is already available in the United States as a pain medicine marketed as Ultram. It has effects similar to morphine, and it may also have effects similar to other drugs like stimulants. The doses of tramadol used in this study are higher than those generally used for the treatment of pain. To be in this study a participant must be a user of opioids (drugs like heroin) and stimulants (drugs like cocaine), but cannot be addicted to either. The person must be between 21-55 years old, and generally healthy. Up to 12 people will take part in this study.
Detailed description
This is a human laboratory study that tests the effects of tramadol as a step in the possible development of this medication as a new treatment for opioid dependence. Tramadol is a mild/moderate mu agonist opioid currently marketed as an analgesic that has a unique profile of effects. One of the primary metabolites of tramadol, mono-O-demethyltramadol (referred to as M1) exerts opioid agonist effects at the mu receptor. In addition, tramadol and M1 produce reuptake blockade of monoamines, and this latter effect may positively influence its analgesic efficacy, in addition to influencing the subjective effects produced by tramadol. Preclinical evidence suggests that tramadol's effects on monoamine reuptake may have antidepressant qualities as well. Given tramadol's diverse pharmacodynamic profile, a systematic characterization of its subjective effects in opioid-experienced subjects would provide valuable information regarding its abuse liability, and its potential utility as a treatment for opioid dependence.
The characterization of an opioid medication's profile can be accomplished through a variety of experimental procedures. One useful procedure for assessing the profile of an opioid is a drug discrimination procedure. In this methodology, subjects are first trained to discriminate reference drugs such as placebo and an opioid agonist, and then administered doses of a novel compound to determine how like (or unlike) it is to the reference training conditions. Our laboratory has a long history of using this drug discrimination methodology to study and to characterize opioids with varying opioid receptor activity profiles. Studies have generally included either two or three training conditions in humans. Using this technique in volunteers, studies have characterized the profile of a number of opioids including (for example) butorphanol, nalbuphine, pentazocine, and buprenorphine.
While most of these studies testing the effects of mixed agonist-antagonist opioids have used an opioid agonist and placebo as the training conditions, tramadol's profile of effects suggests that there may be a non-opioid component of action at serotonin and norepinephrine sites that will be useful to distinguish. In particular, it is of interest to determine the extent to which tramadol is identified as being like a prototypic mu agonist opioid, whether it is substantially identified as being like a non-opioid compound, and if this non-opioid component is related to enhancement of monoamine effects. In order to provide a meaningful non-opioid contrast training condition, this study will compare different doses of tramadol to training conditions of placebo, a mu agonist opioid, and a prototypic stimulant.
Overall, this evaluation will provide a greater understanding of the subjective effect profile of tramadol in comparison to a prototypic mu opioid and a prototypic stimulant. If tramadol is to be useful in the treatment of opioid dependence, a thorough assessment of its subjective effects in experienced opioid and stimulant abusers is warranted.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Tramadol | Active comparator | Drug: tramadoloral dose, once per day |
| Placebo | Placebo comparator | Drug: placebooral dose, once per day |
| hydromorphone | Active comparator | Drug: Hydromorphoneoral dose, once per day |
| methylphenidate | Active comparator | Drug: Methylphenidateoral dose, once per day |
Who may qualify
- Ages
- 21 months to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Study subjects are male and female non-dependent opioid users with active stimulant use.
- Between the ages of 21-55
- In good physical health
- Without significant psychiatric illness besides their drug use.
- Females are required to provide a negative pregnancy test prior to study participation.
Key exclusion criteria (4 listed)
- Subjects are excluded if they have evidence of significant medical (e.g., insulin dependent diabetes mellitus) or psychiatric (e.g., schizophrenia) illness.
- Subjects with a history of seizures will be excluded.
- Persons with current history of significant alcohol or sedative/hypnotic drug use will be excluded from study participation.
- Applicants seeking treatment for their substance abuse will not be admitted to the study, and will be provided information about treatment services available.
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 |
|---|---|---|
| tramadolAlso: Ultramoral dose, once per day | Drug | Tramadol |
| placeboAlso: sugar pilloral dose, once per day | Drug | Placebo |
| HydromorphoneAlso: Dilaudidoral dose, once per day | Drug | hydromorphone |
| MethylphenidateAlso: stimulantoral dose, once per day | Drug | methylphenidate |
Primary outcome
Acquisition of Discrimination Assessed by Accuracy of the Discrimination Test
Time frame: 1 day
The acquisition of discrimination was to test whether volunteers could identify each training drug condition by the correct letter code. Results are the percentage of correct responses with a range of 0% to 100%.
Discrimination Effects Assessed by Operant Responses
Time frame: 1 day
Volunteers emitted operant responses on computer keys that corresponded to the training letter, on a fixed interval 1 second schedule for 8.5 minutes. The range is from 0 to 500 operant responses.
Discrimination Effects Assessed by Point Distribution
Time frame: 1day
In point distribution, volunteers distributed 50 points among three training drug letters depending on how certain they were of the identity of the administrated drug. Maximum total is 50 points.
Discrimination Effects Assessed by Discrete Choice
Time frame: 1 day
During discrete choice, volunteers were given three choices (placebo, hydromorphone, methylphenidate) and were asked to choose which of the training drugs they thought they received. The outcome measure illustrates the percentage of participants who chose either placebo, hydromorphone, or methylphenidate during each drug condition (i.e., Placebo, Hydromorphone 8 mg, Tramadol 50 mg, etc.), ranging from 0-100. The outcome measure represents the percentage of participants who chose either placebo, opioid agonist, or stimulant across each drug condition.
4 secondary outcomes
Physiologic Effects Assessed by the Pharmacological Class Questionnaire
Time frame: Measure at 120 min after drug administration
Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter
Time frame: Measure at 120 min after drug administration
Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS)
Time frame: Measure at 120 min after drug administration
Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS)
Time frame: Measure at 120 min after drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21467190Duke AN, Bigelow GE, Lanier RK, Strain EC. Discriminative stimulus effects of tramadol in humans. J Pharmacol Exp Ther. 2011 Jul;338(1):255-62. doi: 10.1124/jpet.111.181131. Epub 2011 Apr 5.
Related trials for Opioid Abuse
Not yet recruiting
QAIAx - SGI/SI Smart Health Cities: Microcity Enclave Program (Quantum SI/AGI Agency a/k/a AI City Hall Project - UPSTO App Nos. 64/074,526, 64/063,557, 64/105,164, 63/903,181, 63/729,428, 64/125,360; USPTO EO 9424 Assignment ID: 2101042 / ARN: REEL/FRAME: 76481/0026 - OUSD-R&E, Department of War)
Asperger's Disorder, Asperger Disorder
Active, not recruitingObservational study
Cannabis Use and Outcomes in Black and White Patients With Cancer
Cancer
Active, not recruiting
The MOUD Plus Pilot: Counseling and Peer Support to Support Retention for Medically Complex Patients With Opioid Use Disorder Seen In Primary Care
Opioid Dependence, Substance Abuse Disorders
Recruiting
Improving Jail Response to the Overdose Crisis: A Hybrid Trial of Jail ECHO to Improve MOUD Implementation and Public Health Outcomes
Opioid Abuse (Disorder)
RecruitingPhase 4
Abuse Potential of Gabapentin Taken Orally Concomitantly With Oxycodone Hydrochloride in Healthy, Non-Drug-Dependent, Recreational Opioid Users
Healthy
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.
Eric C Strain, M.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing tramadol, Hydromorphone and Methylphenidate in people with Opioid Abuse and Opioid Addiction, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
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 5 inclusion and 4 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 17 Oct 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 United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Acquisition of Discrimination Assessed by Accuracy of the Discrimination Test (time frame: 1 day). The study lists 4 primary outcomes in all. 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 NCT00499746, which also lists 1 linked publication.
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 17 Oct 2017.