Rotigotine + Behavioral Therapy for Cocaine Use Disorder
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Virginia Commonwealth University
Must not be taking: Antipsychotics, Metoclopramide
Disqualifiers: Psychoactive disorders, Seizures, HIV, others
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This is a randomized, double-blind, placebo-controlled phase 2b pilot clinical trial to determine whether non-ergoline D3/D2/D1 dopamine (DA) receptor agonist rotigotine (RTG), in combination with treatment as usual, including individual or group behavioral therapy can a) reduce cocaine use and also b) increase brain activity in frontocortical areas of the brain, and, as a reflection of that - improve top-down cognitive control in persons with cocaine use disorder (CocUD).
Rotigotine is a marketed non-ergoline D3/D2/D1 DA agonist (RTG, Neupro®) in the form of a transdermal patch that is FDA-approved for the treatment of Parkinson's Disease and Restless Legs Syndrome. The premise of this project was based on apparent beneficial effects of RTG in a different human population characterized by executive function (EF) impairment. In light of the deficits in EF common in persons with CocUD, RTG may hold the potential for cognitive improvement in persons with CocUD who are in treatment as usual to both attend to and retain psychoeducation concepts better. In addition, rotigotine may help these individuals in recovery maintain goals better, where goal maintenance is a crucial integrative product of successful EF.
Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications, but you cannot use medications that are not safe to take with rotigotine, like certain antipsychotics or metoclopramide.
What data supports the effectiveness of the drug Rotigotine Transdermal System for treating cocaine use disorder?
There is no direct evidence from the provided research articles supporting the effectiveness of Rotigotine for cocaine use disorder. However, the research highlights the importance of targeting dopamine pathways in treating cocaine addiction, which is relevant since Rotigotine affects dopamine levels.
12345How does the drug Rotigotine differ from other treatments for cocaine use disorder?
Rotigotine is unique because it is a dopamine agonist, meaning it mimics dopamine in the brain, which may help reduce cravings and withdrawal symptoms associated with cocaine use disorder. Unlike other treatments that focus on blocking cocaine's effects or managing withdrawal symptoms, Rotigotine directly stimulates dopamine receptors, potentially offering a novel approach to managing this condition.
14678Eligibility Criteria
Adults aged 18-55 with moderate to severe Cocaine Use Disorder, currently in or starting behavioral therapy for addiction. They must have a positive test for cocaine metabolite and no significant heart issues. Women should be non-pregnant, non-nursing, and using contraception; men advised to use condoms.Inclusion Criteria
Able to understand and comply with study procedures
Women must either be unable to conceive or be using a reliable form of contraception
Have positive urine result for cocaine metabolite benzoylecgonine during at least one screening visit
+7 more
Exclusion Criteria
Recent use of investigational drugs
Pregnant or nursing or not using a reliable form of contraception if able to conceive
I have had seizures or was unconscious for over 30 minutes.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive transdermal rotigotine or placebo patches for approximately six weeks to assess reduction in cocaine use and improvement in cognitive performance
6 weeks
Weekly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing if the Rotigotine patch (approved for Parkinson's & Restless Legs Syndrome) can reduce cocaine use and improve cognitive control when added to standard behavioral therapy compared to a placebo patch.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Active Rotigotine (RTG)Experimental Treatment1 Intervention
Participants who are randomized to the active RTG arm will receive Neupro® RTG patches
Group II: PlaceboPlacebo Group1 Intervention
Participants who are randomized to placebo will receive transdermal patches that match the size and color of active Neupro®.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Virginia Commonwealth UniversityRichmond, VA
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Who Is Running the Clinical Trial?
Virginia Commonwealth UniversityLead Sponsor
National Institute on Drug Abuse (NIDA)Collaborator
References
Recent advances against substance abuse. [2007]Pharmacotherapy for substance abuse is rarely offered to willing recipients without some form of psychosocial support. Pharmacotherapy must match the needs of the patient at the time it is offered, as patients often progress through one or more cycles of use and abstinence. Increasingly, long-acting formulations of agonists and antagonists are being developed as substitution or relapse-prevention products, respectively, in order to aid compliance. Products which target use-reinforcement pathways are starting to progress through clinical trials, as are vaccines that potentially prevent the abused substance reaching the brain. For cocaine abuse, the main focus is on products targeting the dopamine reuptake system.
Effectiveness of adjunct therapies in crack cocaine treatment. [2022]Although intensive outpatient therapy is recommended for treatment of cocaine, psychosocial characteristics associated with crack cocaine abuse are also implicated in attrition from outpatient programs. Acupuncture, medications, and brainwave therapy (biofeedback), have all been used to encourage treatment retention and drug use outcomes. The effectiveness of three adjunct therapies in improving retention and drug use outcomes in intensive outpatient cocaine treatment was tested in a primarily young, indigent African-American sample of crack cocaine users at a community hospital in a low-income, high drug use neighborhood in Houston. Subjects were assigned to receive either neurobehavioral treatment alone or neurobehavioral with one of three adjunct therapies. These included acupuncture, anticraving medication, or brainwave therapy. Comparative results indicated that dosage of any adjunct therapy was associated with days in treatment and standard treatment sessions attended, and that standard treatment sessions attended was associated with negative urinalysis results at follow-up. None of the adjunct therapies were directly associated with drug use outcomes.
Striatal dopamine transporter imaging in nonhuman primates with iodine-123-IPT SPECT. [2016]The regional distribution, kinetics and pharmacological specificity of a new radioiodinated cocaine analog, N-((E)-3-iodopropen-2-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl) tropane ([123I]IPT) were examined in brain SPECT studies (n = 20) of nonhuman primates.
Comparative behavioral pharmacology of cocaine and the selective dopamine uptake inhibitor RTI-113 in the squirrel monkey. [2014]The behavioral effects of 3beta-(4-chlorophenyl)tropane-2beta-carboxylic acid phenyl ester hydrochloride (RTI-113; 0.03-1.0 mg/kg), a selective dopamine uptake inhibitor, were compared with those of cocaine (0.03-3.0 mg/kg) and 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12909; 0.03-3.0 mg/kg) in squirrel monkeys. Intermediate doses of each drug produced significant increases in response rate maintained by a fixed-interval (FI) 300-s schedule of stimulus termination, but RTI-113 was less effective than cocaine or GBR 12909. The order of potency for increasing response rate was RTI-113 >/= cocaine > GBR 12909. In drug time course determinations, RTI-113 and GBR 12909 had longer durations of action than cocaine. RTI-113 substituted completely for cocaine in subjects trained to discriminate cocaine and saline under a two-lever drug-discrimination procedure maintained by food delivery. RTI-113 also reliably maintained self-administration behavior in subjects trained under a second-order FI 900-s schedule of i.v. cocaine delivery. Pretreatment with RTI-113 significantly decreased responding for cocaine at the highest pretreatment dose, but RTI-113 had similar effects on responding maintained by a second-order FI 900-s schedule of stimulus termination. The results indicate that the behavioral pharmacology of RTI-113 is similar to that of cocaine, further implicating a prominent role for dopamine uptake inhibition in the behavioral effects of cocaine. Its longer duration of action in conjunction with less pronounced behavioral-stimulant effects are desirable properties for a substitute pharmacotherapy for cocaine abuse. RTI-113 effectively decreased cocaine self-administration behavior, although its direct rate-altering effects may have contributed to the interactions obtained.
Pharmacotherapy for cocaine-abusing methadone-maintained patients using amantadine or desipramine. [2019]In a double-blind, placebo-controlled 12-week randomized clinical trial, we compared amantadine hydrochloride (300 mg/d; n = 33), desipramine hydrochloride (150 mg/d; n = 30), and placebo (n = 31) in the treatment of cocaine-abusing methadone-maintained patients. Treatment retention and medication compliance were excellent, with more than 75% of the patients completing the full 12-week trial. Although reported cocaine abuse was significantly lower in the medicated groups compared with the placebo group at week 4, this difference became nonsignificant at week 8, and no difference was found in cocaine-free urine samples. Future studies of amantadine and desipramine treatment in these patients should consider alternatives to methadone hydrochloride, such as buprenorphine hydrochloride, and the selection of more homogeneous patient subgroups, such as depressed cocaine abusers.
Agents in development for the management of cocaine abuse. [2018]Cocaine abuse is a serious health problem in many areas of the world, yet there are no proven effective medications for the treatment of cocaine dependence. Preclinical studies suggest that the reinforcing effect of cocaine that promotes its abuse is mediated by blockade of the presynaptic dopamine transporter. This results in increased dopamine activity in the mesolimbic or meso-accumbens dopamine reward system of brain. Development of new medications to treat cocaine dependence has focused on manipulation of this dopamine system, either by direct action on dopamine binding sites (transporter or receptors) or indirectly by affecting other neurotransmitter systems that modulate the dopamine system. In principle, a medication could act via one of three mechanisms: (i) as a substitute for cocaine by producing similar dopamine effects; (ii) as a cocaine antagonist by blocking the binding of cocaine to the dopamine transporter; or (iii) as a modulator of cocaine effects by acting at other than the cocaine binding site. The US National Institute on Drug Abuse has a Clinical Research Efficacy Screening Trial (CREST) programme to rapidly screen existing medications. CREST identified four medications warranting phase II controlled clinical trials: cabergoline, reserpine, sertraline and tiagabine. In addition, disulfiram and selegiline (deprenyl) have been effective and well tolerated in phase II trials. However, selegiline was found ineffective in a recent phase III trial. Promising existing medications probably act via the first or third aforementioned mechanisms. Sustained-release formulations of stimulants such as methylphenidate and amfetamine (amphetamine) have shown promise in a stimulant substitution approach. Disulfiram and selegiline increase brain dopamine concentrations by inhibition of dopamine-catabolising enzymes (dopamine-beta-hydroxylase and monoamine oxidase B, respectively). Cabergoline is a direct dopamine receptor agonist, while reserpine depletes presynaptic stores of dopamine (as well as norepinephrine and serotonin). Sertraline, baclofen and vigabatrin indirectly reduce dopamine activity by increasing activity of neurotransmitters (serotonin and GABA) that inhibit dopamine activity. Promising new medications act via the second or third aforementioned mechanisms. Vanoxerine is a long-acting inhibitor of the dopamine transporter which blocks cocaine binding and reduces cocaine self-administration in animals. Two dopamine receptor ligands that reduce cocaine self-administration in animals are also undergoing phase I human safety trials. Adrogolide is a selective dopamine D(1) receptor agonist; BP 897 is a D(3) receptor partial agonist.A pharmacokinetic approach to treatment would block the entry of cocaine into the brain or enhance its catabolism so that less cocaine reached its site of action. This is being explored in animals using the natural cocaine-metabolising enzyme butyrylcholinesterase (or recombinant versions with enhanced capabilities), catalytic antibodies, and passive or active immunisation to produce anti-cocaine binding antibodies. A recent phase I trial of a "cocaine vaccine" found it to be well tolerated and producing detectable levels of anti-cocaine antibodies for up to 9 months after immunisation.
Modafinil in the treatment of crack-cocaine dependence in the Netherlands: Results of an open-label randomised controlled feasibility trial. [2018]Crack-cocaine dependence is a serious disorder with no approved pharmacological treatment. Modafinil is a promising medication with increased cocaine abstinence and reduced craving in some previous studies. In the present study, we examined the acceptance, safety and potential benefits of modafinil as an add-on treatment to cognitive behavioural therapy (CBT) in crack-cocaine dependent patients.
Pharmacological adjuncts in the treatment of opioid and cocaine addicts. [2013]Addiction consists of a complex neuropharmacologic behavioral cycle. The positive reinforcement of the drug and the negative reinforcement of withdrawal serve to drive the behavior of obtaining and ingesting the drug. The pharmacological adjuncts that are available today work by interfering with one or another part of the cycle. The alpha 2-adrenergic agonists, such as clonidine and guanabenz, act to block noradrenergic activity in the locus coeruleus and therefore block the negative reinforcement of opioid withdrawal. Naltrexone, on the other hand, works by preventing the positive reinforcement of administered opioids by preventing them from binding to the opioid receptor. In the case of cocaine addiction, most of the adjuncts currently in use focus on decreasing the severity of the immediate withdrawal symptoms. These agents potentiate dopaminergic transmission and in so doing tend to counter the dopamine depletion effect of prolonged cocaine use. Bromocriptine is the best known and probably the most effective member of this class. It may be that neuroleptics or naltrexone will prove to decrease reinforcement of cocaine use. However, the hazards of long-term neuroleptic use make it unlikely that they will be widely used for this purpose. Desipramine and perhaps other antidepressants may have a special role in treating cocaine addiction: They may prove to have some long-term prophylactic value and prevent relapse in recovering addicts. This ability may stem from the antidepressant action or it may involve a more specific action on dopaminergic transmission. These pharmacological agents may be very effective for certain purposes, such as relieving withdrawal symptoms. However, since they only act on one part of the addiction cycle, they can never be considered complete treatment by themselves. Of course, the use of all of these agents requires the voluntary cooperation of the patient. Therefore, the basis of the treatment of addictive illness continues to be the peer group and other types of interpersonal interactions. However, these pharmacological adjuncts may serve to make treatment easier, shorter and less expensive, and they may improve overall success rates. Consequently, they are of great value in the present and they can serve as models for the development of more effective agents in the future.