Opioid Related DisordersPhase 1/2NCT01188421

Medications Development for Drug Abuse Disorders

A Phase 1/2 study testing Buprenorphine/naloxone, Clonidine and Tramadol ER in people with Opioid Related Disorders and Opioid Dependence, run by Johns Hopkins University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a study of tramadol as an agent for short-term opioid withdrawal treatment. A randomized, double blind clinical trial comparing the efficacy and safety of tramadol to clonidine and buprenorphine in the short-term treatment of opioid withdrawal will be conducted. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Opioid Related Disorders, Opioid Dependence, Opioid Addiction
What is being tested?: Buprenorphine/naloxone, Clonidine and Tramadol ER
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 106 participants
Where: 1 siteUnited States
Study dates: Oct 2010to Jun 2015
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 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Participants in this study will be males and females between the ages of 18 and 60 years.
Applicants must be opioid dependent based upon the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (SCID); in addition, they must have an opioid positive urine during the screening process (or have evidence of opioid withdrawal).
They must be healthy, with no significant medical illnesses (e.g., insulin dependent diabetes), and without significant psychiatric illness (e.g., schizophrenia) besides their drug dependence.
Females will have a pregnancy test prior to study enrollment, and if found to be pregnant will be excluded and referred to a substance abuse program for pregnant women (the Center for Addiction and Pregnancy) on the campus.
Volunteers will also be excluded if they have pre-admission hypotension (due to the use of clonidine in the study).
Applicants with a history of seizures (including substance-related seizures, such as alcohol withdrawal related) will be excluded.
Alcohol and/or sedative dependence will be specific exclusionary criteria (given the small risk of seizures associated with tramadol use).
Allergies to any of the study medications will be grounds for exclusion.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

Johns Hopkins University (BPRU) Bayview Campus
Baltimore, Maryland, 21224

Other trials in United States

About this study

Conditions: Opioid Related Disorders, Opioid Dependence, Opioid Addiction
Being tested: Buprenorphine/naloxone, Clonidine, Tramadol ER
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.

Buprenorphine/naloxoneDrug
Also called Suboxone
up to 8/2 mg Sublingual (SL) per day
ClonidineDrug
Also called Catapres
up to 0.8 mg per day (oral)
Tramadol ERDrug
Also called Ultram
up to 600 mg per day

Study groups in NCT01188421
Study group	Role	What they receive
buprenorphine	Active comparator	Sublingual buprenorphine/naloxone tablets (or placebo) Receives: Drug: Buprenorphine/naloxone
clonidine	Active comparator	Oral clonidine tablets (or placebo) Receives: Drug: Clonidine
tramadol ER	Experimental	Oral tramadol tablets (or placebo) Receives: Drug: Tramadol ER

What is being measured

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

Mean Ratings on Clinical Opiate Withdrawal Scale (COWS) Measure of Withdrawal During Double-blind Taper (7-days) and Post-taper (7-days) Period.
Outcomes represent mean peak withdrawal as rated on the Clinical Opiate Withdrawal Scale (COWS) total score. Withdrawal was collected 7 times daily and daily peak values were identified for each participant and averaged together as a function of group. Primary outcomes were mean peak results from the 7-day taper period and first 7 days post-taper. The COWS is an 11-item observer-rated measure of opioid withdrawal severity. Items are rated on individual Likert scales and the total score range is 0-47. Higher values indicate more severe withdrawal.
Measured: 14 days total

Timeline

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

Oct 2010Jun 2015

First posted25 Aug 2010 (estimated)
Study startOct 2010
Primary completionJun 2015
Study completionJun 2015

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 Related DisordersStudies of the same condition, open and under way.
More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
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: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 106 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01188421
Sponsor's protocol ID: NIDA-018125
Other IDs: NA_00037871, R01DA018125, DPMC
Status last verified: Jun 2017
First submitted: 11 Aug 2010
Last updated: 6 Jul 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Dunn KE, Tompkins DA, Bigelow GE, Strain EC. Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial. JAMA Psychiatry. 2017 Sep 1;74(9):885-893. doi: 10.1001/jamapsychiatry.2017.1838.
PubMed 28700791

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Chronic Pain, Pain

All Opioid Related Disorders trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Jul 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: NCT01188421
Acronym / sponsor ID: NIDA-018125
Conditions: Opioid Related Disorders, Opioid Dependence, Opioid Addiction
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 106 participants (actual)
Lead sponsor: Johns Hopkins UniversityUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: Oct 2010
Primary completion: Jun 2015 (actual)
Study completion: Jun 2015 (actual)
First posted: 25 Aug 2010 (estimated)
Results: Posted 6 Jul 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
buprenorphine	Active comparator	Drug: Buprenorphine/naloxoneSublingual buprenorphine/naloxone tablets (or placebo)
clonidine	Active comparator	Drug: ClonidineOral clonidine tablets (or placebo)
tramadol ER	Experimental	Drug: Tramadol EROral tramadol tablets (or placebo)

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (8 listed)

Participants in this study will be males and females between the ages of 18 and 60 years.
Applicants must be opioid dependent based upon the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (SCID); in addition, they must have an opioid positive urine during the screening process (or have evidence of opioid withdrawal).
They must be healthy, with no significant medical illnesses (e.g., insulin dependent diabetes), and without significant psychiatric illness (e.g., schizophrenia) besides their drug dependence.
Females will have a pregnancy test prior to study enrollment, and if found to be pregnant will be excluded and referred to a substance abuse program for pregnant women (the Center for Addiction and Pregnancy) on the campus.
Volunteers will also be excluded if they have pre-admission hypotension (due to the use of clonidine in the study).

Key exclusion criteria (0 listed)

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
Buprenorphine/naloxoneAlso: Suboxoneup to 8/2 mg Sublingual (SL) per day	Drug	buprenorphine
ClonidineAlso: Catapresup to 0.8 mg per day (oral)	Drug	clonidine
Tramadol ERAlso: Ultramup to 600 mg per day	Drug	tramadol ER

Primary outcome

Mean Ratings on Clinical Opiate Withdrawal Scale (COWS) Measure of Withdrawal During Double-blind Taper (7-days) and Post-taper (7-days) Period.
Time frame: 14 days total
Outcomes represent mean peak withdrawal as rated on the Clinical Opiate Withdrawal Scale (COWS) total score. Withdrawal was collected 7 times daily and daily peak values were identified for each participant and averaged together as a function of group. Primary outcomes were mean peak results from the 7-day taper period and first 7 days post-taper. The COWS is an 11-item observer-rated measure of opioid withdrawal severity. Items are rated on individual Likert scales and the total score range is 0-47. Higher values indicate more severe withdrawal.

Results and safety

Results posted to the registry on 6 Jul 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Buprenorphine	31	28
Tramadol ER	36	26
Clonidine	36	22

Primary outcome: Mean Ratings on Clinical Opiate Withdrawal Scale (COWS) Measure of Withdrawal During Double-blind Taper (7-days) and Post-taper (7-days) Period.

Time frame: 14 days total. Mean (Standard Error). Unit: units on a scale

Measure	Buprenorphine n = 31	Tramadol ER n = 36	Clonidine n = 36
Taper Day 1	7.79 (1.68)	8.41 (0.70)	8.28 (0.71)
Taper Day 2	6.16 (2.03)	6.10 (0.72)	8.00 (0.46)
Taper Day 3	4.76 (1.77)	3.77 (0.35)	5.85 (0.66)
Taper Day 4	4.21 (1.77)	4.25 (0.52)	4.70 (0.57)
Taper Day 5	4.31 (2.11)	3.25 (0.37)	3.32 (0.41)
Taper Day 6	4.06 (1.63)	3.39 (0.45)	3.57 (0.57)
Taper Day 7	3.51 (1.28)	3.69 (0.53)	3.86 (0.64)
Post Taper Day 1	4.82 (1.62)	3.36 (0.44)	3.27 (0.37)

Buprenorphine vs Tramadol ER vs Clonidine: F-value for main effect of Group: 1.310, p = .275, ANOVA
Buprenorphine vs Tramadol ER vs Clonidine: F-value for main effect of Phase: 3.570, p = 0.03, ANOVA
Buprenorphine vs Tramadol ER vs Clonidine: F-value for the main effect of Group x P: 2.030, p = 0.092, ANOVA

Population analysed: Repeated measures ANOVA

Adverse events

Time frame: Adverse events are reported from the Taper and Post-Taper periods (approximately 18-19 days). No Adverse Events reported from Stabilization phase (7-10 day period) since this occurred prior to primary experimental manipulation and randomization to study drug (clonidine, tramadol, buprenorphine).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Buprenorphine	0 of 31 (0%)	28 of 31 (90.3%)	0 of 31
Tramadol ER	0 of 36 (0%)	31 of 36 (86.1%)	0 of 36
Clonidine	0 of 36 (0%)	32 of 36 (88.9%)	0 of 36

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28700791Dunn KE, Tompkins DA, Bigelow GE, Strain EC. Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial. JAMA Psychiatry. 2017 Sep 1;74(9):885-893. doi: 10.1001/jamapsychiatry.2017.1838.

Related trials for Opioid Related Disorders

Not yet recruitingEarly Phase 1
Pain Sensitivity, Alcohol-Induced Analgesia, and Heavy Drinking in Individuals With Opioid Use Disorder
Opioid Use Disorder, Alcohol Intoxication
Enrolling by invitationObservational study
Development of an Interview-Informed Timeline Follow-Back (TLFB) for Opioid Use in the Era of Fentanyl
Substance Use Disorders (SUDs)
Active, not recruitingObservational study
Cannabis Use and Outcomes in Black and White Patients With Cancer
Cancer
RecruitingObservational study
Outcome Inference in the Sensory Preconditioning Task in Opioid-Use Disorder
Opioid-Related Disorders, Drug Addiction
RecruitingPhase 2
A Study of Cebranopadol for Opioid Withdrawal Symptoms in Adults With Chronic Pain
Chronic Pain, Pain

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 Buprenorphine/naloxone, Clonidine and Tramadol ER in people with Opioid Related Disorders and Opioid Dependence, run by Johns Hopkins University 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 8 inclusion and 0 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 6 Jul 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. 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 6 Jul 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?

Mean Ratings on Clinical Opiate Withdrawal Scale (COWS) Measure of Withdrawal During Double-blind Taper (7-days) and Post-taper (7-days) Period. (time frame: 14 days total). 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 NCT01188421, 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 6 Jul 2017.