Cocaine Dependence
Conditions
Keywords
Cocaine, immunotherapy, vaccination, antibody, addiction, dependence
Brief summary
Clinical data demonstrate that a cocaine vaccine (TA-CD: Celtic Pharmaceutical) produces selective anti-cocaine antibodies, yet the impact of these antibodies on cocaine's direct effects is unknown. The objective of this human laboratory study was to measure the relationship between antibody titers and the effects of smoked cocaine on ratings of intoxication, craving and cardiovascular effects. Cocaine-dependent volunteers not seeking drug treatment spend 2 nights per week for 13 weeks inpatient where the effects of cocaine (0, 25, 50 mg) are determined prior to vaccination and at weekly intervals thereafter. Vaccinations occur at weeks 1, 3, 5 and 9.
Detailed description
I do not desire to provide a more extensive description.
Interventions
BIOLOGICALCocaine vaccine (TA-CD)
TA-CD (82,360 μg; IM) were administered at weeks 1, 3, 5 and 9.
Sponsors
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Meets DSM-IV criteria for current cocaine dependence. The volunteer may meet criteria for other substance abuse, but not dependence (other than nicotine). 2. Primary route of cocaine administration is smoking. 3. Age 21-45. 4. Females must be surgically sterilized or post- menopausal 5. Able to give informed consent, and comply with study procedures.
Exclusion criteria
1. Dependence on substances other than cocaine or nicotine. 2. Judged to be noncompliant with study protocol. 3. History of autoimmune disease, immune deficiency or hypersensitivity to other vaccines. An HIV test must be negative. 4. Currently uses drugs intravenously 5. Currently taking any psychotropic medication 6. Laboratory tests that are clinically unacceptable to the study physician (BP \> 140/90; BUN, creatinine, LFTs \> 1.5 ULN; hematocrit \< 34 for women, \< 36 for men) 7. Blood or blood products given in the three months prior to vaccination 8. Other vaccines, including flu vaccine, given within 30 days of screening. 9. Ongoing active infection 10. Currently taking immunosuppressives -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Intoxication | 13 weeks | Visual Analogue Scale ratings (0-100mm) of the Good Drug Effect cluster (Good Drug Effect, High, Stimulated) over 13 weeks as a function of cocaine dose (25mg or 50mg). Participants (n=10) were evenly divided into High Antibody (AB) and Low Antibody (AB) groups based on their peak antibody levels at Week 13. Higher numbers indicate more agreement with the statements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Cardiovascular Effects | 13 weeks | Heart rate levels in Week 3 and Week 13 as a function of cocaine dose in High and Low antibody groups. Participants (n=10) were evenly divided into High Antibody (AB) and Low Antibody (AB) groups based on their peak antibody levels at Week 13. Higher numbers indicate higher heart rates. |
| Plasma Cocaine | 13 weeks | Plasma cocaine levels in Week 3 and Week 13 as a function of cocaine dose in High and Low AB groups. Participants (n=10) were evenly divided into High Antibody (AB) and Low Antibody (AB) groups based on their peak antibody levels at Week 13. Higher numbers indicate higher plasma levels of cocaine. |
Countries
United States
Participant flow
Recruitment details
Cocaine-dependent research volunteers who were explicitly not interested in treatment for their cocaine use signed a consent form approved by NYSPI IRB, which described the procedures and outlined the possible risks, including administration of an experimental vaccine and smoked cocaine.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Vaccine (82μg) All participants were vaccinated four times: in week 1, 3, 5, and 9.
Cocaine vaccine (TA-CD): TA-CD (82 μg; IM) were administered at weeks 1, 3, 5 and 9. | 4 |
| High Dose Vaccine (360μg) All participants were vaccinated four times: in week 1, 3, 5, and 9.
Cocaine vaccine (TA-CD): TA-CD (360 μg; IM) were administered at weeks 1, 3, 5 and 9. | 6 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Family emergency | 0 | 1 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 2 |
Baseline characteristics
| Characteristic | High Dose Vaccine (360μg) | Total | Low Dose Vaccine (82μg) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 10 Participants | 4 Participants |
| Age, Continuous | 39 years STANDARD_DEVIATION 1.9 | 39 years STANDARD_DEVIATION 1.9 | 38 years STANDARD_DEVIATION 1.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 1 Participants |
| Region of Enrollment United States | 6 participants | 10 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 6 |
| other Total, other adverse events | 0 / 4 | 0 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 |
Outcome results
Primary
Cocaine Intoxication
Visual Analogue Scale ratings (0-100mm) of the Good Drug Effect cluster (Good Drug Effect, High, Stimulated) over 13 weeks as a function of cocaine dose (25mg or 50mg). Participants (n=10) were evenly divided into High Antibody (AB) and Low Antibody (AB) groups based on their peak antibody levels at Week 13. Higher numbers indicate more agreement with the statements.
Time frame: 13 weeks
Population: Peak plasma antibody levels were highly variable. Thus, participants (n=10) were evenly divided into High Antibody (AB) and Low Antibody (AB) groups for analysis, based on their peak antibody levels at Week 13, rather than by the dose of vaccine received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Week 1 Low Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 59 units on a scale | Standard Error 9 |
| Week 1 Low Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 83 units on a scale | Standard Error 4 |
| Week 3 Low Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 68 units on a scale | Standard Error 8 |
| Week 3 Low Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 51 units on a scale | Standard Error 8 |
| Week 5 Low Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 45 units on a scale | Standard Error 9 |
| Week 5 Low Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 61 units on a scale | Standard Error 7 |
| Week 7 Low Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 44 units on a scale | Standard Error 8 |
| Week 7 Low Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 58 units on a scale | Standard Error 8 |
| Week 9 Low Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 42 units on a scale | Standard Error 8 |
| Week 9 Low Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 58 units on a scale | Standard Error 8 |
| Week 11 Low Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 38 units on a scale | Standard Error 8 |
| Week 11 Low Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 50 units on a scale | Standard Error 10 |
| Week 13 Low Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 40 units on a scale | Standard Error 7 |
| Week 13 Low Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 60 units on a scale | Standard Error 8 |
| Week 1 High Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 62 units on a scale | Standard Error 8 |
| Week 1 High Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 58 units on a scale | Standard Error 8 |
| Week 3 High Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 50 units on a scale | Standard Error 8 |
| Week 3 High Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 32 units on a scale | Standard Error 8 |
| Week 5 High Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 48 units on a scale | Standard Error 4 |
| Week 5 High Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 29 units on a scale | Standard Error 0 |
| Week 7 High Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 23 units on a scale | Standard Error 4 |
| Week 7 High Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 48 units on a scale | Standard Error 8 |
| Week 9 High Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 29 units on a scale | Standard Error 3 |
| Week 9 High Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 42 units on a scale | Standard Error 6 |
| Week 11 High Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 19 units on a scale | Standard Error 3 |
| Week 11 High Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 48 units on a scale | Standard Error 5 |
| Week 13 High Antibody | Cocaine Intoxication | Good Drug Effect of 25 mg cocaine | 10 units on a scale | Standard Error 2 |
| Week 13 High Antibody | Cocaine Intoxication | Good Drug Effect of 50 mg cocaine | 25 units on a scale | Standard Error 5 |
Secondary
Cocaine Cardiovascular Effects
Heart rate levels in Week 3 and Week 13 as a function of cocaine dose in High and Low antibody groups. Participants (n=10) were evenly divided into High Antibody (AB) and Low Antibody (AB) groups based on their peak antibody levels at Week 13. Higher numbers indicate higher heart rates.
Time frame: 13 weeks
Population: Peak plasma antibody levels were highly variable. Thus, participants (n=10) were evenly divided into High Antibody (AB) and Low Antibody (AB) groups for analysis, based on their peak antibody levels at Week 13, rather than by the dose of vaccine received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Week 1 Low Antibody | Cocaine Cardiovascular Effects | Week 3 | 75 BPM | Standard Error 3 |
| Week 1 Low Antibody | Cocaine Cardiovascular Effects | Week 13 | 76 BPM | Standard Error 2 |
| Week 3 Low Antibody | Cocaine Cardiovascular Effects | Week 3 | 82 BPM | Standard Error 2 |
| Week 3 Low Antibody | Cocaine Cardiovascular Effects | Week 13 | 99 BPM | Standard Error 2 |
| Week 5 Low Antibody | Cocaine Cardiovascular Effects | Week 3 | 92 BPM | Standard Error 1 |
| Week 5 Low Antibody | Cocaine Cardiovascular Effects | Week 13 | 102 BPM | Standard Error 2 |
| Week 7 Low Antibody | Cocaine Cardiovascular Effects | Week 3 | 79 BPM | Standard Error 1.5 |
| Week 7 Low Antibody | Cocaine Cardiovascular Effects | Week 13 | 82 BPM | Standard Error 2 |
| Week 9 Low Antibody | Cocaine Cardiovascular Effects | Week 3 | 98 BPM | Standard Error 3 |
| Week 9 Low Antibody | Cocaine Cardiovascular Effects | Week 13 | 101 BPM | Standard Error 5 |
| Week 11 Low Antibody | Cocaine Cardiovascular Effects | Week 3 | 109 BPM | Standard Error 4 |
| Week 11 Low Antibody | Cocaine Cardiovascular Effects | Week 13 | 122 BPM | Standard Error 6 |
Secondary
Plasma Cocaine
Plasma cocaine levels in Week 3 and Week 13 as a function of cocaine dose in High and Low AB groups. Participants (n=10) were evenly divided into High Antibody (AB) and Low Antibody (AB) groups based on their peak antibody levels at Week 13. Higher numbers indicate higher plasma levels of cocaine.
Time frame: 13 weeks
Population: Peak plasma antibody levels were highly variable. Thus, participants (n=10) were evenly divided into High Antibody (AB) and Low Antibody (AB) groups for analysis, based on their peak antibody levels at Week 13, rather than by the dose of vaccine received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Week 1 Low Antibody | Plasma Cocaine | Week 3 | 5 ng/mL | Standard Error 0.2 |
| Week 1 Low Antibody | Plasma Cocaine | Week 13 | 25 ng/mL | Standard Error 2 |
| Week 3 Low Antibody | Plasma Cocaine | Week 3 | 125 ng/mL | Standard Error 8 |
| Week 3 Low Antibody | Plasma Cocaine | Week 13 | 110 ng/mL | Standard Error 5 |
| Week 5 Low Antibody | Plasma Cocaine | Week 3 | 160 ng/mL | Standard Error 10 |
| Week 5 Low Antibody | Plasma Cocaine | Week 13 | 200 ng/mL | Standard Error 20 |
| Week 7 Low Antibody | Plasma Cocaine | Week 3 | 20 ng/mL | Standard Error 2 |
| Week 7 Low Antibody | Plasma Cocaine | Week 13 | 25 ng/mL | Standard Error 2 |
| Week 9 Low Antibody | Plasma Cocaine | Week 3 | 145 ng/mL | Standard Error 20 |
| Week 9 Low Antibody | Plasma Cocaine | Week 13 | 175 ng/mL | Standard Error 10 |
| Week 11 Low Antibody | Plasma Cocaine | Week 3 | 260 ng/mL | Standard Error 40 |
| Week 11 Low Antibody | Plasma Cocaine | Week 13 | 325 ng/mL | Standard Error 50 |