Cocaine Use DisordersEarly Phase 1NCT01739192
A Novel Anti-Obesity Drug Combination as a Pharmacotherapy for Cocaine Dependence
A Early Phase 1 study testing Bupropion in people with Cocaine Use Disorders, run by Craig Rush at 1 site in United States.
Trial summary
The research proposed in this application will determine the initial efficacy, safety and tolerability of a novel drug combination, bupropion and naltrexone, as a pharmacotherapy for cocaine dependence. A rigorous, inpatient human laboratory study will be conducted. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Cocaine Use Disorders
- What is being tested?
- Bupropion
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to Jun 2018
- Phase
- Early 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Recent cocaine use
Who cannot join
- Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant.
- Current or past histories of substance abuse or dependence that are deemed by the study physicians to interfere with study completion.
- History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation.
- Females not currently using effective birth control.
- Contraindications to cocaine, bupropion or naltrexone,
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kentucky Medical Center
Lexington, Kentucky, 40536-0086
About this study
The research proposed in this application will determine the initial efficacy, safety and tolerability of a novel drug combination, bupropion and naltrexone, as a pharmacotherapy for cocaine dependence. A rigorous, inpatient human laboratory study will be conducted. The proposed study is innovative and important because it will provide the impetus for the conduct of double blind, placebo-controlled trials to further demonstrate the efficacy of bupropion-naltrexone combinations for managing cocaine dependence.
Read the detailed description
Cocaine (COC) dependence is a significant public health concern. A widely effective pharmacotherapy has not yet been identified for COC dependence. Innovative strategies are needed to identify an effective pharmacotherapy for COC dependence. Testing medications effective for disorders that share neurobiological substrates with drug dependence, for example, could yield treatments for managing COC dependence.
Obesity is also a significant public health concern. Although obesity and COC dependence are typically considered distinct clinical entities, both diseases involve perturbations of central biogenic amine and/or hypothalamic-melanocortin systems. The obesity epidemic has spurred development of medications to promote weight loss. A combination of bupropion (BUP) and naltrexone (NTX) is effective for obesity. The overarching goal of this application is to demonstrate the initial efficacy, safety, and tolerability of BUP-NTX combinations for COC dependence. A mixed-model experiment will be conducted in which separate cohorts of non-treatment-seeking, COC-dependent participants will be randomized to different maintenance doses of NTX (i.e., NTX is a between-subject factor). Participants (N=12) in each NTX cohort will be maintained concurrently on BUP (i.e., BUP is a within-subject factor). The reinforcing effects of intranasal COC will be determined after participants in each NTX cohort are maintained for 4-7 days on each of the BUP doses (i.e., COC is a within-subject factor). COC (0, 40 and 80 mg) will be tested with multiple dose combinations of BUP (0, 100, 200, 400 mg/day) and NTX (0, 25, 50 mg/day). The proposed study will also identify the optimal dose combination of BUP and NTX that most effectively attenuates the reinforcing effects of COC.
This research will provide critical information regarding the initial efficacy and optimal doses of a novel drug combination, BUP and NTX, for COC dependence, which will enhance the probability of success when advanced to a clinical trial. Innovations of the proposed research include: 1) testing a combination of marketed drugs that demonstrated modest efficacy when tested as mono-therapies; 2) the use of a sophisticated drug self-administration procedure; 3) providing the impetus for the conduct of a Phase II clinical trial to further demonstrate the efficacy of BUP-NTX combinations for COC dependence; and 4) demonstrating the initial efficacy and optimal doses of a combination of commercially available drugs, as opposed to waiting for novel molecules to be available for testing in humans, thereby impacting clinical research and practice more quickly. In these ways, the proposed project will shift the current clinical research paradigm in pharmacotherapy development and have a significant impact on the treatment of COC dependence.
- Conditions
- Cocaine Use Disorders
- Being tested
- Bupropion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BupropionDrug
Subjects will be maintained on oral bupropion or placebo during the study.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Placebo comparator | Placebo oral daily for approximately six (6) weeks. Receives: Drug: Bupropion |
| Arm 2 | Experimental | Naltrexone (25 mg) oral daily for approximately six (6) weeks. Receives: Drug: Bupropion |
| Arm 3 | Experimental | Naltrexone (50 mg) oral daily for approximately six (6) weeks. Receives: Drug: Bupropion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reinforcing Effects
The reinforcing effects of cocaine will be determined using a self-administration procedure in which subjects choose to take previously sampled doses. Reinforcing effects are measured during maintenance on placebo, bupropion, naltrexone, and bupropion-naltrexone combinations.
Measured: Twelve (12) times over approximately six (6) weeks inpatient admission.
Secondary outcomes (2)
Subjective effects
Subjects will complete subjective effects measures during sessions while they are admitted to our inpatient unit. These items will ask about drug effects and general mood.
Measured: Twelve (12) times over approximately six (6) weeks inpatient admission.
Physiological and side effects.
Physiological and side effects measures will be completed daily while subjects are admitted to our inpatient unit. Physiological measures included heart rate and blood pressure. Side effects questions will query subjects about common effects of centrally active medications.
Measured: Daily over approximately six (6) weeks inpatient admission.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2012 (estimated)
- Study startJan 2013
- Primary completionDec 2017
- Study completionJun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cocaine Use DisordersStudies 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Craig Rush
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor-investigator, Craig Rush, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01739192
- Sponsor's protocol ID
- R01DA032254
- Other IDs
- R01DA032254
- Status last verified
- Jun 2018
- First submitted
- 27 Nov 2012
- Last updated
- 26 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Novel Anti-Obesity Drug Combination as a Pharmacotherapy for Cocaine Dependence
- ClinicalTrials.gov ID
- NCT01739192
- Acronym / sponsor ID
- R01DA032254
- Conditions
- Cocaine Use Disorders
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Craig RushUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Jan 2013
- Primary completion
- Dec 2017 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 3 Dec 2012 (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 research proposed in this application will determine the initial efficacy, safety and tolerability of a novel drug combination, bupropion and naltrexone, as a pharmacotherapy for cocaine dependence. A rigorous, inpatient human laboratory study will be conducted. The proposed study is innovative and important because it will provide the impetus for the conduct of double blind, placebo-controlled trials to further demonstrate the efficacy of bupropion-naltrexone combinations for managing cocaine dependence.
Detailed description
Cocaine (COC) dependence is a significant public health concern. A widely effective pharmacotherapy has not yet been identified for COC dependence. Innovative strategies are needed to identify an effective pharmacotherapy for COC dependence. Testing medications effective for disorders that share neurobiological substrates with drug dependence, for example, could yield treatments for managing COC dependence.
Obesity is also a significant public health concern. Although obesity and COC dependence are typically considered distinct clinical entities, both diseases involve perturbations of central biogenic amine and/or hypothalamic-melanocortin systems. The obesity epidemic has spurred development of medications to promote weight loss. A combination of bupropion (BUP) and naltrexone (NTX) is effective for obesity. The overarching goal of this application is to demonstrate the initial efficacy, safety, and tolerability of BUP-NTX combinations for COC dependence. A mixed-model experiment will be conducted in which separate cohorts of non-treatment-seeking, COC-dependent participants will be randomized to different maintenance doses of NTX (i.e., NTX is a between-subject factor). Participants (N=12) in each NTX cohort will be maintained concurrently on BUP (i.e., BUP is a within-subject factor). The reinforcing effects of intranasal COC will be determined after participants in each NTX cohort are maintained for 4-7 days on each of the BUP doses (i.e., COC is a within-subject factor). COC (0, 40 and 80 mg) will be tested with multiple dose combinations of BUP (0, 100, 200, 400 mg/day) and NTX (0, 25, 50 mg/day). The proposed study will also identify the optimal dose combination of BUP and NTX that most effectively attenuates the reinforcing effects of COC.
This research will provide critical information regarding the initial efficacy and optimal doses of a novel drug combination, BUP and NTX, for COC dependence, which will enhance the probability of success when advanced to a clinical trial. Innovations of the proposed research include: 1) testing a combination of marketed drugs that demonstrated modest efficacy when tested as mono-therapies; 2) the use of a sophisticated drug self-administration procedure; 3) providing the impetus for the conduct of a Phase II clinical trial to further demonstrate the efficacy of BUP-NTX combinations for COC dependence; and 4) demonstrating the initial efficacy and optimal doses of a combination of commercially available drugs, as opposed to waiting for novel molecules to be available for testing in humans, thereby impacting clinical research and practice more quickly. In these ways, the proposed project will shift the current clinical research paradigm in pharmacotherapy development and have a significant impact on the treatment of COC dependence.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Placebo comparator | Drug: BupropionPlacebo oral daily for approximately six (6) weeks. |
| Arm 2 | Experimental | Drug: BupropionNaltrexone (25 mg) oral daily for approximately six (6) weeks. |
| Arm 3 | Experimental | Drug: BupropionNaltrexone (50 mg) oral daily for approximately six (6) weeks. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Recent cocaine use
Key exclusion criteria (5 listed)
- Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant.
- Current or past histories of substance abuse or dependence that are deemed by the study physicians to interfere with study completion.
- History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation.
- Females not currently using effective birth control.
- Contraindications to cocaine, bupropion or naltrexone,
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 |
|---|---|---|
| BupropionSubjects will be maintained on oral bupropion or placebo during the study. | Drug | Arm 1, Arm 2, Arm 3 |
Primary outcome
Reinforcing Effects
Time frame: Twelve (12) times over approximately six (6) weeks inpatient admission.
The reinforcing effects of cocaine will be determined using a self-administration procedure in which subjects choose to take previously sampled doses. Reinforcing effects are measured during maintenance on placebo, bupropion, naltrexone, and bupropion-naltrexone combinations.
2 secondary outcomes
Subjective effects
Time frame: Twelve (12) times over approximately six (6) weeks inpatient admission.
Physiological and side effects.
Time frame: Daily over approximately six (6) weeks inpatient admission.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2018.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Bupropion in people with Cocaine Use Disorders, run by Craig Rush 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 1 inclusion and 5 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 26 Jun 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 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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Reinforcing Effects (time frame: Twelve (12) times over approximately six (6) weeks inpatient admission.). 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 26 Jun 2018.