Development of Ivermectin for Alcohol Use Disorders
Study Details
Study Description
Brief Summary
Current pharmacotherapies for alcohol use disorders (AUDs) have limited efficacy. Thus, the development of effective treatments for AUDs represents an important public health objective. Repositioning, i.e. using existing approved drugs for other indications, represents a fast and economically feasible approach for drug development. Ivermectin (IVM) is an FDA-approved antiparasitic medication that can significantly reduce alcohol intake in mice, suggesting that it may be useful in the treatment of AUDs in humans. The goal of this project is to provide key clinical evidence that IVM can be repositioned as a novel therapeutic agent to treat AUDs.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Current pharmacotherapies for alcohol use disorders (AUDs) have limited efficacy. Thus, the development of effective treatments for AUDs represents an important public health objective. Repositioning, i.e. using existing approved drugs for other indications, represents a fast and economically feasible approach for drug development. Ivermectin (IVM) is an FDA-approved antiparasitic medication that can significantly reduce alcohol intake in mice, suggesting that it may be useful in the treatment of AUDs in humans. The goal of this project is to provide key clinical evidence that IVM can be repositioned as a novel therapeutic agent to treat AUDs. We will enroll 10 alcohol dependent individuals in a placebo-controlled randomized pilot safety trial of IVM (30 mg orally once) over a 2-day (1-night) inpatient stay at the UCLA CTRC and employ a well-characterized battery of behavioral paradigms (i.e., alcohol administration and cue exposure). The goals of the study are to test: (a) the safety of combining IVM, at a dose currently shown to be safe in humans (30 mg), with moderate doses of alcohol (0.08 g/dl); and (b) whether IVM reduces the reinforcing effects of alcohol during alcohol administration and whether it reduces alcohol craving during cue exposure, as compared to placebo.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ivermectin Ivermectin 30 mg single dose |
Drug: Ivermectin
Ivermectin is a semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum antiparasitic avermectin.
Other Names:
Drug: Alcohol
Other Names:
|
| Placebo Comparator: Sugar pill Matched placebo, single dose |
Drug: Placebo
Matched placebo
Other Names:
Drug: Alcohol
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Heart Rate [Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl]
Heart rate (measured in beats per minute; BPM) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). During the infusion, the times for collecting HR will vary based on how long it takes participants to reach the targeted BrACs.
- Systolic Blood Pressure [Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl]
Blood pressure (measured in mmHg) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). Blood pressure is measured at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post-medication administration; and during alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl. During the infusion, the times for collecting BP will vary based on how long it takes participants to reach the targeted BrACs.
- Diastolic Blood Pressure [Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl]
Blood pressure (measured in mmHg) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). Blood pressure is measured at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post-medication administration; and during alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl. During the infusion, the times for collecting BP will vary based on how long it takes participants to reach the targeted BrACs.
- Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) [During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.]
Subjective effects of alcohol will be measured using the Alcohol Urge Questionnaire (AUQ), which consists of 8 items associated with urge to drink alcohol, rated on a 7 point scale (1 = strongly disagree, 7 = strongly agree).
- Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "Feel" Subscale [During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.]
Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Do you feel any drug effects?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects).
- Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "Like" Subscale [During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.]
Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Do you like the effects you are feeling right now?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects).
- Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "More" Subscale [During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.]
Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Would you like more of the drug right now?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects).
- Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "High" Subscale [During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.]
Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Are you high?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects).
- Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale [During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.]
Subjective effects of alcohol will be measured using the Biphasic Alcohol Effects Scale (BAES) , which consists of 14 items designed to capture the stimulant and sedative effects of alcohol, each rated on an 11-point scale (0 = not at all, 10 = extremely). The total score for the Stimulant Subscale ranges from 0 to 70. Mean scores across all subjects are reported below.
- Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale [During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.]
Subjective effects of alcohol will be measured using the Biphasic Alcohol Effects Scale (BAES) , which consists of 14 items designed to capture the stimulant and sedative effects of alcohol, each rated on an 11-point scale (0 = not at all, 10 = extremely). The total score for the Sedative Subscale ranges from 0 to 70. Mean scores across subjects are reported below.
- Cue-induced Craving Using the Alcohol Urge Questionnaire (AUQ) [6 hours post-medication administration]
Cue-induced craving will be measured using the Alcohol Urge Questionnaire (AUQ), which consists of 8 items associated with urge to drink alcohol, rated on a 7 point scale (0 = strongly disagree, 6 = strongly agree). Item scores were averaged and the total score also ranges from 0-6.
- Adverse Effects [During alcohol infusion at BrAC = 0.00, 0.04, 0.08 g/dl]
Adverse effects will be monitored to determine the safe of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl) using the Systematic Assessment for Treatment Emergent Effects (SAFTEE). The SAFTEE is a 24-item checklist in which the participant can identify whether a symptom is present (yes/no), its severity (mild, moderate, severe) and whether it was caused by the medication (yes/no). Data below represents a count of individual adverse effects reported on the SAFTEE during the alcohol infusion.
Secondary Outcome Measures
- Ivermectin Pharmacokinetics: Peak Concentration (Cmax) [Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48]
This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Maximum plasma concentration (Cmax), measured in ng/mL, provided below.
- Ivermectin Pharmacokinetics: Time to Cmax (Tmax) [Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48]
This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Time to Cmax (Tmax), measured in hours, provided below.
- Ivermectin Pharmacokinetics: Area Under the Time-concentration Curve (AUC) [Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48]
This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Area under the time-concentration curve (AUC) from 0 to 48 hours after IVM administration, provided below.
- Ivermectin Pharmacokinetics: Half-life (T1/2) [Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48]
This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Half-life of ivermectin (T1/2), measured in hours, provided below.
- Stress-induced Alcohol Craving [pre-post exposure to an imaginal stress script]
Alcohol Urge Questionnaire (AUQ)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
age between 21 and 65;
-
meet current DSM-V diagnostic criteria for an alcohol use disorder
Exclusion Criteria:
-
current treatment for alcohol problems, a history of treatment in the 30 days before enrollment or current treatment seeking;
-
a current (last 12 months) DSM-V diagnosis of dependence on any psychoactive substances other than alcohol and nicotine;
-
a lifetime DSM-IV diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder;
-
positive urine screen for narcotics, amphetamines, or sedative hypnotics;
-
serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-R);
-
pregnancy, nursing, or refusal to use reliable method of birth control (if female);
-
a medical condition that may interfere with safe study participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes);
-
AST, ALT, or GGT ≥ 3 times upper normal limit;
-
currently on prescription medication that contraindicates use of IVN;
-
any other circumstances that, in the opinion of the investigators, compromises participant safety.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCLA Addictions Laboratory | Los Angeles | California | United States | 90095 |
Sponsors and Collaborators
- University of California, Los Angeles
Investigators
- Principal Investigator: Lara Ray, PhD, University of California, Los Angeles
- Study Director: Daniel Roche, PhD, University of California, Los Angeles
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- IVM
- UL1TR000124
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | IVM 30mg First, Then Placebo | Placebo First, Then IVM 30 mg |
|---|---|---|
| Arm/Group Description | First Intervention, Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. Second Intervention, Placebo: Single dose sugar pill, matched to active medication. | First Intervention, Placebo: Single dose sugar pill, matched to active medication. Second Intervention, Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Period Title: First Intervention (1 Day) | ||
| STARTED | 5 | 6 |
| COMPLETED | 5 | 6 |
| NOT COMPLETED | 0 | 0 |
| Period Title: First Intervention (1 Day) | ||
| STARTED | 5 | 6 |
| COMPLETED | 5 | 6 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | IVM 30mg; Placebo |
|---|---|
| Arm/Group Description | Ivermectin (IVM): Single dose (30 mg) of a semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. Placebo: Single dose sugar pill matched to active medication. |
| Overall Participants | 11 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
38.82
(11.39)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
2
18.2%
|
| Male |
9
81.8%
|
| Meets criteria for DSM-V AD (participants) [Number] | |
| Number [participants] |
11
100%
|
Outcome Measures
| Title | Heart Rate |
|---|---|
| Description | Heart rate (measured in beats per minute; BPM) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). During the infusion, the times for collecting HR will vary based on how long it takes participants to reach the targeted BrACs. |
| Time Frame | Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 | 11 |
| 0 hours post-med |
64.57
(9.74)
|
68.36
(20.47)
|
| 0.5 hours post-med |
66.82
(10.91)
|
62.82
(11.46)
|
| 1 hour post-med |
66.09
(12.01)
|
64.27
(11.60)
|
| 2 hours post-med |
65.18
(13.88)
|
61.18
(11.03)
|
| 4 hours post-med |
66.73
(10.60)
|
61.55
(12.36)
|
| 6 hours post-med |
63.27
(12.66)
|
59.73
(12.62)
|
| 8 hours post-med |
66.36
(13.44)
|
62.18
(11.76)
|
| 10 hours post-med |
64.70
(14.33)
|
62.64
(10.19)
|
| 12 hours post-med |
72.45
(13.41)
|
73.64
(9.31)
|
| 16 hours post-med |
61.18
(12.08)
|
58.09
(10.97)
|
| 24 hours post-med |
62.55
(11.09)
|
64.64
(10.58)
|
| 48 hours post-med |
69.18
(10.15)
|
69.45
(12.49)
|
| BrAC = 0 |
63.09
(12.69)
|
61.00
(11.80)
|
| BrAC = 0.02 |
67.27
(14.00)
|
63.36
(9.00)
|
| BrAC = 0.04 |
66.91
(10.89)
|
61.82
(9.16)
|
| BrAC = 0.06 |
66.64
(12.83)
|
63.09
(9.82)
|
| BrAC = 0.08 |
66.36
(12.37)
|
61.27
(8.21)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, IVM 30mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0563 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Systolic Blood Pressure |
|---|---|
| Description | Blood pressure (measured in mmHg) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). Blood pressure is measured at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post-medication administration; and during alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl. During the infusion, the times for collecting BP will vary based on how long it takes participants to reach the targeted BrACs. |
| Time Frame | Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 | 11 |
| 0 hours post-med |
121
(11.10)
|
111.64
(17.35)
|
| 0.5 hours post-med |
118.64
(10.67)
|
117
(12.61)
|
| 1 hour post-med |
120.64
(11.44)
|
116.27
(11.80)
|
| 2 hours post-med |
121.27
(10.59)
|
118.27
(12.48)
|
| 4 hours post-med |
117
(12.15)
|
111.91
(12.85)
|
| 6 hours post-med |
117.27
(16.17)
|
119.55
(15.33)
|
| 8 hours post-med |
115.18
(13.50)
|
107.27
(10.56)
|
| 10 hours post-med |
116.70
(13.49)
|
114.09
(13.63)
|
| 12 hours post-med |
116.09
(9.17)
|
119.63
(7.99)
|
| 16 hours post-med |
115.64
(17.19)
|
115.45
(8.85)
|
| 24 hours post-med |
122
(11.61)
|
122.73
(8.72)
|
| 48 hours post-med |
122.72
(8.67)
|
121.09
(9.47)
|
| BrAC = 0 |
120.27
(15.07)
|
114.36
(12.75)
|
| BrAC = 0.02 |
118.55
(10.56)
|
114.18
(12.34)
|
| BrAC = 0.04 |
116.55
(12.36)
|
111.27
(10.72)
|
| BrAC = 0.06 |
112.73
(11.40)
|
115.18
(14.08)
|
| BrAC = 0.08 |
112.45
(12.60)
|
108.82
(11.50)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, IVM 30mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0342 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Diastolic Blood Pressure |
|---|---|
| Description | Blood pressure (measured in mmHg) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). Blood pressure is measured at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post-medication administration; and during alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl. During the infusion, the times for collecting BP will vary based on how long it takes participants to reach the targeted BrACs. |
| Time Frame | Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 | 11 |
| 0 hours post-med |
79.64
(10.23)
|
75.55
(13.20)
|
| 0.5 hours post-med |
77.45
(11.44)
|
75.18
(11.12)
|
| 1 hour post-med |
78.82
(10.30)
|
74.91
(10.43)
|
| 2 hours post-med |
79.91
(8.80)
|
76.64
(12.14)
|
| 4 hours post-med |
74.55
(10.82)
|
72.18
(10.91)
|
| 6 hours post-med |
75.36
(14.49)
|
74.55
(11.22)
|
| 8 hours post-med |
72.55
(10.05)
|
69.45
(10.46)
|
| 10 hours post-med |
75.30
(11.88)
|
73.82
(12.60)
|
| 12 hours post-med |
73.64
(9.84)
|
77.27
(6.44)
|
| 16 hours post-med |
72.82
(12.69)
|
73.18
(8.81)
|
| 24 hours post-med |
76.09
(12.39)
|
78.09
(10.23)
|
| 48 hours post-med |
80.55
(10.96)
|
81.55
(10.49)
|
| BrAC = 0 |
78.18
(11.57)
|
74.36
(12.49)
|
| BrAC = 0.02 |
77.91
(10.01)
|
73.73
(10.96)
|
| BrAC = 0.04 |
77.55
(10.71)
|
72.91
(11.89)
|
| BrAC = 0.06 |
75.27
(9.31)
|
74.00
(12.13)
|
| BrAC = 0.08 |
71.91
(10.90)
|
72.73
(10.75)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, IVM 30mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1597 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) |
|---|---|
| Description | Subjective effects of alcohol will be measured using the Alcohol Urge Questionnaire (AUQ), which consists of 8 items associated with urge to drink alcohol, rated on a 7 point scale (1 = strongly disagree, 7 = strongly agree). |
| Time Frame | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 | 11 |
| BrAC = 0.00 |
2.58
(1.74)
|
2.90
(2.04)
|
| BrAC = 0.02 |
3.14
(1.64)
|
3.27
(1.65)
|
| BrAC = 0.04 |
3.02
(1.64)
|
3.19
(1.60)
|
| BrAC = 0.06 |
2.73
(2.00)
|
2.60
(1.60)
|
| BrAC = 0.08 |
2.83
(1.79)
|
2.91
(1.87)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, IVM 30mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7617 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "Feel" Subscale |
|---|---|
| Description | Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Do you feel any drug effects?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects). |
| Time Frame | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 | 11 |
| BrAC = 0.00 |
1.36
(2.66)
|
0.91
(1.30)
|
| BrAC = 0.02 |
2.73
(2.45)
|
3.45
(2.21)
|
| BrAC = 0.04 |
3.82
(2.75)
|
4.82
(3.03)
|
| BrAC = 0.06 |
4.45
(3.48)
|
5.36
(3.33)
|
| BrAC = 0.08 |
5.27
(3.29)
|
6.36
(2.80)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, IVM 30mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.93 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "Like" Subscale |
|---|---|
| Description | Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Do you like the effects you are feeling right now?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects). |
| Time Frame | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 | 11 |
| BrAC = 0.00 |
4.09
(1.70)
|
4.09
(2.02)
|
| BrAC = 0.02 |
5.36
(1.63)
|
5.36
(3.20)
|
| BrAC = 0.04 |
6.18
(2.52)
|
5.55
(2.95)
|
| BrAC = 0.06 |
6.64
(2.98)
|
6.36
(3.44)
|
| BrAC = 0.08 |
6.45
(3.33)
|
6.27
(3.50)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, IVM 30mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.95 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "More" Subscale |
|---|---|
| Description | Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Would you like more of the drug right now?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects). |
| Time Frame | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 | 11 |
| BrAC = 0.00 |
1.64
(2.25)
|
3.18
(4.00)
|
| BrAC = 0.02 |
4.91
(4.09)
|
6.27
(4.52)
|
| BrAC = 0.04 |
5.45
(3.96)
|
6.00
(3.95)
|
| BrAC = 0.06 |
5.00
(3.92)
|
5.64
(4.03)
|
| BrAC = 0.08 |
5.27
(4.25)
|
5.55
(4.78)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, IVM 30mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.43 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "High" Subscale |
|---|---|
| Description | Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Are you high?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects). |
| Time Frame | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 | 11 |
| BrAC = 0.00 |
0.91
(1.70)
|
0.09
(0.30)
|
| BrAC = 0.02 |
2.64
(2.29)
|
3.27
(2.01)
|
| BrAC = 0.04 |
4.00
(2.93)
|
5.36
(2.66)
|
| BrAC = 0.06 |
4.91
(3.56)
|
5.73
(2.57)
|
| BrAC = 0.08 |
5.09
(3.62)
|
6.00
(2.79)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, IVM 30mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.06 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale |
|---|---|
| Description | Subjective effects of alcohol will be measured using the Biphasic Alcohol Effects Scale (BAES) , which consists of 14 items designed to capture the stimulant and sedative effects of alcohol, each rated on an 11-point scale (0 = not at all, 10 = extremely). The total score for the Stimulant Subscale ranges from 0 to 70. Mean scores across all subjects are reported below. |
| Time Frame | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 | 11 |
| BrAC = 0.00 |
18.09
(13.37)
|
17.36
(12.99)
|
| BrAC = 0.02 |
20.00
(11.91)
|
23.73
(14.29)
|
| BrAC = 0.04 |
21.73
(15.04)
|
20.09
(13.32)
|
| BrAC = 0.06 |
25.91
(19.03)
|
22.64
(15.74)
|
| BrAC = 0.08 |
26.18
(20.17)
|
20.91
(15.00)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, IVM 30mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.21 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale |
|---|---|
| Description | Subjective effects of alcohol will be measured using the Biphasic Alcohol Effects Scale (BAES) , which consists of 14 items designed to capture the stimulant and sedative effects of alcohol, each rated on an 11-point scale (0 = not at all, 10 = extremely). The total score for the Sedative Subscale ranges from 0 to 70. Mean scores across subjects are reported below. |
| Time Frame | During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 | 11 |
| BrAC = 0.00 |
14.18
(14.67)
|
10.64
(9.97)
|
| BrAC = 0.02 |
11.00
(13.10)
|
13.09
(14.80)
|
| BrAC = 0.04 |
10.91
(14.72)
|
16.00
(15.75)
|
| BrAC = 0.06 |
15.27
(17.41)
|
16.73
(19.22)
|
| BrAC = 0.08 |
15.27
(18.93)
|
16.64
(17.32)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, IVM 30mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.09 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Cue-induced Craving Using the Alcohol Urge Questionnaire (AUQ) |
|---|---|
| Description | Cue-induced craving will be measured using the Alcohol Urge Questionnaire (AUQ), which consists of 8 items associated with urge to drink alcohol, rated on a 7 point scale (0 = strongly disagree, 6 = strongly agree). Item scores were averaged and the total score also ranges from 0-6. |
| Time Frame | 6 hours post-medication administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 | 11 |
| Mean (Standard Deviation) [scores on a scale] |
3.59
(1.69)
|
4.07
(1.34)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, IVM 30mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.99 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Title | Adverse Effects |
|---|---|
| Description | Adverse effects will be monitored to determine the safe of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl) using the Systematic Assessment for Treatment Emergent Effects (SAFTEE). The SAFTEE is a 24-item checklist in which the participant can identify whether a symptom is present (yes/no), its severity (mild, moderate, severe) and whether it was caused by the medication (yes/no). Data below represents a count of individual adverse effects reported on the SAFTEE during the alcohol infusion. |
| Time Frame | During alcohol infusion at BrAC = 0.00, 0.04, 0.08 g/dl |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | Placebo (BrAC = 0.00) | Placebo (BrAC = 0.04) | Placebo (BrAC = 0.08) | IVM 30mg (BrAC = 0.00) | IVM 30mg (BrAC = 0.04) | IVM 30mg (BrAC = 0.08) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. Timepoint is at beginning of alcohol infusion when BrAC is still 0.00. | Single dose sugar pill, matched to active medication. Timepoint is during alcohol infusion when BrAC has reached 0.04. | Single dose sugar pill, matched to active medication. Timepoint is during alcohol infusion when BrAC has reached 0.08. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. Timepoint is at beginning of alcohol infusion when BrAC is still 0.00. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. Timepoint is during alcohol infusion when BrAC has reached 0.04. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. Timepoint is during alcohol infusion when BrAC has reached 0.08. |
| Measure Participants | 11 | 11 | 11 | 11 | 11 | 11 |
| Abdominal pain/cramps |
0
|
1
|
1
|
0
|
0
|
0
|
| Yellow eyes |
0
|
0
|
0
|
0
|
0
|
0
|
| Nausea or vomiting |
0
|
0
|
0
|
0
|
0
|
0
|
| Irritability or anger |
1
|
0
|
0
|
0
|
0
|
0
|
| Increased desire for sex |
1
|
0
|
1
|
1
|
2
|
1
|
| Nervousness |
1
|
0
|
0
|
1
|
0
|
0
|
| Ringing in the ears |
0
|
0
|
0
|
0
|
0
|
0
|
| Decrease in appetite |
0
|
0
|
0
|
0
|
0
|
0
|
| Depression |
0
|
0
|
0
|
0
|
0
|
0
|
| Fatigue |
1
|
2
|
2
|
1
|
1
|
2
|
| Difficulty in staying awake |
3
|
3
|
4
|
3
|
2
|
2
|
| Increase in appetite |
0
|
1
|
3
|
1
|
2
|
4
|
| Blurred vision |
1
|
1
|
1
|
0
|
1
|
1
|
| Drowsiness |
2
|
4
|
2
|
2
|
4
|
5
|
| Headache |
0
|
0
|
0
|
0
|
1
|
0
|
| Night sweats |
0
|
0
|
0
|
0
|
0
|
0
|
| Mental confusion |
0
|
0
|
0
|
0
|
0
|
0
|
| Anxiety |
0
|
0
|
0
|
0
|
1
|
0
|
| Joint or muscle pain |
0
|
0
|
0
|
0
|
0
|
0
|
| Dizziness |
0
|
0
|
0
|
0
|
1
|
2
|
| Sexual problems |
0
|
0
|
0
|
0
|
0
|
0
|
| Difficulty sleeping |
0
|
0
|
0
|
0
|
0
|
0
|
| Fever or chills |
0
|
0
|
0
|
0
|
0
|
0
|
| Decreased desire for sex |
0
|
0
|
0
|
0
|
0
|
0
|
| Title | Ivermectin Pharmacokinetics: Peak Concentration (Cmax) |
|---|---|
| Description | This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Maximum plasma concentration (Cmax), measured in ng/mL, provided below. |
| Time Frame | Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | IVM 30mg |
|---|---|
| Arm/Group Description | Ivermectin (IVM): Single dose (30 mg) of a semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [ng/mL] |
406.03
(398.36)
|
| Title | Ivermectin Pharmacokinetics: Time to Cmax (Tmax) |
|---|---|
| Description | This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Time to Cmax (Tmax), measured in hours, provided below. |
| Time Frame | Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | IVM 30mg |
|---|---|
| Arm/Group Description | Ivermectin (IVM): Single dose (30 mg) of a semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [hours] |
9.09
(3.62)
|
| Title | Ivermectin Pharmacokinetics: Area Under the Time-concentration Curve (AUC) |
|---|---|
| Description | This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Area under the time-concentration curve (AUC) from 0 to 48 hours after IVM administration, provided below. |
| Time Frame | Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized subjects included. |
| Arm/Group Title | IVM 30mg |
|---|---|
| Arm/Group Description | Ivermectin (IVM): Single dose (30 mg) of a semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [ng*h/mL] |
5078
(4258)
|
| Title | Ivermectin Pharmacokinetics: Half-life (T1/2) |
|---|---|
| Description | This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Half-life of ivermectin (T1/2), measured in hours, provided below. |
| Time Frame | Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | IVM 30mg |
|---|---|
| Arm/Group Description | Ivermectin (IVM): Single dose (30 mg) of a semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [hours] |
15.75
(6.86)
|
| Title | Stress-induced Alcohol Craving |
|---|---|
| Description | Alcohol Urge Questionnaire (AUQ) |
| Time Frame | pre-post exposure to an imaginal stress script |
Outcome Measure Data
| Analysis Population Description |
|---|
| The stress paradigm (pre-post exposure to an imaginal stress script) was not implemented from the outset of the study due to feasibility reasons. In particular, the investigators were concerned that the timing of the stress exposure might contaminate the effects of the alcohol administration. |
| Arm/Group Title | Placebo | IVM 30mg |
|---|---|---|
| Arm/Group Description | Single dose sugar pill, matched to active medication. | Ivermectin (IVM): Single dose (30 mg) of semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum anti parasitic avermectin. |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | IVM 30mg | Placebo | ||
| Arm/Group Description | Ivermectin 30 mg single dose Ivermectin: Ivermectin is a semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum antiparasitic avermectin. Alcohol | Matched placebo, single dose Placebo: sugar pill Alcohol | ||
All Cause Mortality |
||||
| IVM 30mg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| IVM 30mg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | 0/11 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| IVM 30mg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | 0/11 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Lara Ray |
|---|---|
| Organization | UCLA Department of Psychology |
| Phone | 310-794-5383 |
| lararay@psych.ucla.edu |
- IVM
- UL1TR000124