HBPL Study of the Impact of the NK1 Antagonist Aprepitant

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01176591
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 13
• Location: 1
• Arms: 2
• Duration (Months): 39
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The proposed research will focus on investigating the determinants and consequences of CAD via measurement of physiological, behavioral and subjective effects of physiologic and psychologic stress cues in CAD volunteers in the laboratory, and through examination of the effects of the effects of Aprepitant, an NK1 antagonist, on the above effects. This study will examine the effects of the above stress cues on cocaine and alcohol craving under acute Aprepitant dosing, and under placebo conditions. The study is a within-subjects crossover design using 24 subjects.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence; Alcohol Dependence	Drug: Placebo session 1, Aprepitant session 2; Drug: Placebo session 1, Placebo session 2	Phase 2

Detailed Description

Non treatment seeking subjects with DSM IV cocaine and alcohol dependence were included. Subjects received double-blind acute dosing of 80 mg of aprepitant (Emend) at session start, or matched placebo. During each session subjects were exposed to one of two types of stressors, one stressor per session, presented in counterbalanced order across participants. The Physiologic stress was the cold-pressor task. Subjects immersed their hand in cold water for up to 3 minutes. The psychological stress was the Trier Social Stress Test it was completed in 25 minutes: 5 min audio taped instructions, 10 min to mentally prepare for their performance tasks, 5 min to complete a public speaking task and 5 min to complete a mental arithmetic task. Outcome measures included: Alcohol Craving measured by visual analog scale, cocaine craving measured by visual analog scale and The Multiple Choice Procedure. Each assessment was done during study screening, and then at multiple times during each study session.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Human Behavioral Pharmacology Laboratory (HBPL) Study of the Impact of the NK1 Antagonist Aprepitant (Emend®) on Stress-Induced Cocaine and Alcohol Craving
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo Session 1, Aprepitant Session 2 Participants receive placebo in session 1 and Aprepitant in session 2 of a psychological stressor presentation and receive placebo in session 1 and Aprepitant in session 2 of a physiological stressor presentation. Participants take Aprepitant (80 mg) or placebo tablets for 7 days prior to each session.	Drug: Placebo session 1, Aprepitant session 2; placebo in session 1, Aprepitant 80 mg in session 2, oral administration.; Other Names: Aprepitant
Placebo Comparator: Placebo Session 1, Placebo Session 2 Participants receive placebo in session 1 and placebo in session 2 of a psychological stressor presentation and receive placebo in session 1 and placebo in session 2 of a physiological stressor presentation. Participants take placebo tablets for 7 days prior to each session. The placebo group is used for analysis purposes in order to control for any order effects found in the Experimental group.	Drug: Placebo session 1, Placebo session 2; Placebo, one per session, oral administration; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Cocaine Craving as Measured on the Visual Analog Scale (VAS) 1 [Session 1]

   The VAS is a 100 mm line anchored at both ends. Participants mark where on the line their craving falls, with closer to 0 indicating less craving, and closer to 100 indicating more craving. Data are analyzed by using a ruler to determine the actual mm value of the participant mark.

2. Alcohol Craving as Measured by the Visual Analog Scale (VAS) 1 [Session 1]

   The VAS is a 100 mm line anchored at both ends. Participants mark where on the line their craving falls, with closer to 0 indicating less craving, and closer to 100 indicating more craving. Data are analyzed by using a ruler to determine the actual mm value of the participant mark.

3. Cocaine Craving as Measured on the Visual Analog Scale (VAS) 2 [Session 2]

   The VAS is a 100 mm line anchored at both ends. Participants mark where on the line their craving falls, with closer to 0 indicating less craving, and closer to 100 indicating more craving. Data are analyzed by using a ruler to determine the actual mm value of the participant mark.

4. Alcohol Craving as Measured by the Visual Analog Scale (VAS) 2 [Session 2]

   The VAS is a 100 mm line anchored at both ends. Participants mark where on the line their craving falls, with closer to 0 indicating less craving, and closer to 100 indicating more craving. Data are analyzed by using a ruler to determine the actual mm value of the participant mark.

Secondary Outcome Measures

1. Multiple Choice Procedure (MCP) 1 [Session 1]

   The MCP measures the relative reinforcing value of a hypothetical single dose of cocaine, as compared to various monetary values. The lower the monetary value where participants switch from preferring cocaine to preferring money, the less value they place on cocaine. MCP findings of cocaine devaluation typically correlate with cocaine abstinence in clinical trials.

2. Multiple Choice Procedure (MCP) 2 [Session 2]

   The MCP measures the relative reinforcing value of a hypothetical single dose of cocaine, as compared to various monetary values. The lower the monetary value where participants switch from preferring cocaine to preferring money, the less value they place on cocaine. MCP findings of cocaine devaluation typically correlate with cocaine abstinence in clinical trials.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Male or female and 18 years of age to 60

2. The subject has used cocaine and alcohol at least once per month for at least the past year, and has used cocaine and alcohol within 30 days prior to signing consent.

3. Live within a commutable distance of the Treatment Research Center (TRC) at the Penn/VA Center for Studies of Addiction, University of Pennsylvania. We define this to be a distance within the service area of Septa, within an hour drive, or a distance that both the patient and Principal Investigator (PI) find acceptable.

4. Understands and signs the informed consent.

Exclusion Criteria:

1. Meets Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria for current dependence on any substance other than nicotine, cocaine ,alcohol or marijuana

2. Subjects who test positive on the urine drug screen for any illicit drugs other than cocaine and marijuana during screening will be allowed a single retest. Those individuals who test positive for amphetamine during screening, given that they provide a copy of a prescription, will only be included if they can safely discontinue amphetamine use for the duration of the study. Subjects will need to provide a urine free of all illicit drugs other than cocaine and marijuana at study onset to be randomized. Subjects who test positive for any drugs other than marijuana prior to a study session will be allowed a single retest and a chance to reschedule their session. If the subject tests positive for any drug other than marijuana at the retest, their participation in the study will be terminated.

3. Subjects who meet current or lifetime DSM-IV criteria for bipolar affective disorder, schizophrenia, or any psychotic disorder

4. Current severe psychiatric symptoms- (e.g., psychosis, dementia, suicidal or homicidal ideation, mania or depression requiring anti-depressant therapy) as diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID), the Hamilton Anxiety Rating Scale (Ham A), and Hamilton Rating Scale for Depression (HAM-D).

5. Individuals scoring > 10 on the Hamilton Rating Scale for Depression (HAM-D).

6. Use of any investigational medication within the past 30 days.

7. Concomitant treatment with psychotropic medications or prescription opioids.

8. Concomitant use of any one of the following drugs or classes of drugs:

Reserpine Verapamil theophylline, trimethoprim, cimetidine, haloperidol, benzodiazepines, or antiepileptic drugs (AEDs).

1. Patients with a known hypersensitivity to aprepitant.

2. Patients with severe concurrent illnesses such as bronchospastic disease, hyperthyroidism, diabetes mellitus.

3. Patients with known AIDS or other serious illnesses that may require hospitalization during the study.

4. Female subjects who are pregnant or lactating, or female subjects of child-bearing potential who are not using acceptable methods of birth control; acceptable methods of birth control include:

Barrier method (diaphragm or condom) with spermicide Intrauterine progesterone contraceptive system Levonorgestrel implant Medroxyprogesterone acetate contraceptive injection, or Oral contraceptives.

1. Patients with impaired renal function, as indicated by corrected creatinine clearance below 60 ml/min as determined by the modified Cockcroft equation (CDC, 1986).

2. An unacceptable liver panel or liver function tests (LFTs) that may be indicative of hepatic dysfunction.

3. Clinical laboratory tests (e.g., complete blood count (CBC), blood chemistries, urinalysis) outside normal limits, as determined by the study PI.

4. History of significant heart disease or dysfunction (e.g., an arrhythmia which required medication, Wolff Parkinson -White Syndrome, angina pectoris, documented history of myocardial infarction, heart failure).

5. Electrocardiography (EKG) indicative of 1st degree heart block, sinus tachycardia, left-axis deviation, non-specific ST or T-wave changes.

6. History of chest pain associated with cocaine use that prompted a visit to a physician.

7. Any medical or psychological condition that could jeopardize the subject's safe participation in the trial as determined by the PI.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania, Treatment Research Center	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• National Institute on Drug Abuse (NIDA)

Investigators

• Study Director: Kyle M Kampman, MD, Perelman School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01176591
• Other Study ID Numbers: 811184; K01DA025073
• First Posted: Aug 6, 2010
• Last Update Posted: Jul 15, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of Pennsylvania: Cocaine and alcohol dependence (CAD)
• Additional relevant MeSH terms: Alcoholism; Cocaine-Related Disorders; Aprepitant; Fosaprepitant

Study Results

Participant Flow

Arm/Group Title	Placebo Session 1, Aprepitant Session 2	Placebo in Session 1, Placebo in Session 2
Arm/Group Description	Placebo in session 1; Aprepitant: 80 mg in session 2, oral administration.	Placebo, one per session, oral administration
Period Title: Session 1
STARTED	10	3
COMPLETED	10	3
NOT COMPLETED	0	0
Period Title: Session 1
STARTED	10	3
COMPLETED	10	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo Session 1, Aprepitant Session 2	Placebo Session1, Placebo Session 2	Total
Arm/Group Description	Placebo in session 1; Aprepitant: 80 mg in session 2, oral administration.	Placebo, one per session, oral administration	Total of all reporting groups
Overall Participants	10	3	13
Age, Customized (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	3 100%	13 100%
>=65 years	0 0%	0 0%	0 0%
Sex/Gender, Customized (Count of Participants)
Female	2 20%	1 33.3%	3 23.1%
Male	8 80%	2 66.7%	10 76.9%
Region of Enrollment (participants) [Number]
United States	10 100%	3 100%	13 100%

Outcome Measures

1. Primary Outcome

Title	Cocaine Craving as Measured on the Visual Analog Scale (VAS) 1
Description	The VAS is a 100 mm line anchored at both ends. Participants mark where on the line their craving falls, with closer to 0 indicating less craving, and closer to 100 indicating more craving. Data are analyzed by using a ruler to determine the actual mm value of the participant mark.
Time Frame	Session 1

Outcome Measure Data

Analysis Population Description

Comparing Placebo to Placebo

Arm/Group Title	Placebo Session 1, Aprepitant Session 2	Placebo Session 1, Placebo Session 2
Arm/Group Description	Placebo in session 1; Aprepitant: 80 mg in session 2, oral administration.	Placebo in Session 1, Placebo in Session 2, oral administration
Measure Participants	10	3
Mean (Full Range) [units on a scale]	19	48

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Session 1, Aprepitant Session 2, Placebo Session 1, Placebo Session 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Alcohol Craving as Measured by the Visual Analog Scale (VAS) 1
Description	The VAS is a 100 mm line anchored at both ends. Participants mark where on the line their craving falls, with closer to 0 indicating less craving, and closer to 100 indicating more craving. Data are analyzed by using a ruler to determine the actual mm value of the participant mark.
Time Frame	Session 1

Outcome Measure Data

Analysis Population Description

Comparing Placebo to Placebo

Arm/Group Title	Placebo Session 1, Aprepitant Session 2	Placebo Session 1, Placebo Session 2
Arm/Group Description	Placebo session 1, Aprepitant 80 mg session 2, oral administration.	Placebo, one per session, oral administration
Measure Participants	10	3
Mean (Full Range) [units on a scale]	26.25	38.92

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Session 1, Aprepitant Session 2, Placebo Session 1, Placebo Session 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	t-test, 2 sided
	Comments

3. Primary Outcome

Title	Cocaine Craving as Measured on the Visual Analog Scale (VAS) 2
Description	The VAS is a 100 mm line anchored at both ends. Participants mark where on the line their craving falls, with closer to 0 indicating less craving, and closer to 100 indicating more craving. Data are analyzed by using a ruler to determine the actual mm value of the participant mark.
Time Frame	Session 2

Outcome Measure Data

Analysis Population Description

Comparing Aprepitant to Placebo

Arm/Group Title	Placebo Session 1, Aprepitant Session 2	Placebo Session 1, Placebo Session 2
Arm/Group Description	Placebo in session 1; Aprepitant: 80 mg in session 2, oral administration.	Placebo in Session 1, Placebo in Session 2, oral administration
Measure Participants	10	3
Mean (Full Range) [units on a scale]	20	4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Session 1, Aprepitant Session 2, Placebo Session 1, Placebo Session 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments
	Method	t-test, 2 sided
	Comments

4. Primary Outcome

Title	Alcohol Craving as Measured by the Visual Analog Scale (VAS) 2
Description	The VAS is a 100 mm line anchored at both ends. Participants mark where on the line their craving falls, with closer to 0 indicating less craving, and closer to 100 indicating more craving. Data are analyzed by using a ruler to determine the actual mm value of the participant mark.
Time Frame	Session 2

Outcome Measure Data

Analysis Population Description

Comparing Aprepitant to Placebo

Arm/Group Title	Placebo Session 1, Aprepitant Session 2	Placebo Session 1, Placebo Session 2
Arm/Group Description	Placebo session 1, Aprepitant 80 mg session 2, oral administration.	Placebo, one per session, oral administration
Measure Participants	10	3
Mean (Full Range) [units on a scale]	33.22	0.17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Session 1, Aprepitant Session 2, Placebo Session 1, Placebo Session 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.039
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Multiple Choice Procedure (MCP) 1
Description	The MCP measures the relative reinforcing value of a hypothetical single dose of cocaine, as compared to various monetary values. The lower the monetary value where participants switch from preferring cocaine to preferring money, the less value they place on cocaine. MCP findings of cocaine devaluation typically correlate with cocaine abstinence in clinical trials.
Time Frame	Session 1

Outcome Measure Data

Analysis Population Description

Comparing Placebo to Placebo

Arm/Group Title	Placebo Session 1, Aprepitant Session 2	Placebo Session 1, Placebo Session 2
Arm/Group Description	Placebo session 1, Aprepitant 80 mg session 2, oral administration.	Placebo, one per session, oral administration
Measure Participants	10	3
Mean (Full Range) [dollars]	8.58	17.33

6. Secondary Outcome

Title	Multiple Choice Procedure (MCP) 2
Description	The MCP measures the relative reinforcing value of a hypothetical single dose of cocaine, as compared to various monetary values. The lower the monetary value where participants switch from preferring cocaine to preferring money, the less value they place on cocaine. MCP findings of cocaine devaluation typically correlate with cocaine abstinence in clinical trials.
Time Frame	Session 2

Outcome Measure Data

Analysis Population Description

Comparing Aprepitant to Placebo

Arm/Group Title	Placebo Session 1, Aprepitant Session 2	Placebo Session 1, Placebo Session 2
Arm/Group Description	Placebo session 1, Aprepitant 80 mg session 2, oral administration.	Placebo, one per session, oral administration
Measure Participants	10	3
Mean (Full Range) [dollars]	7.59	17.33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Session 1, Aprepitant Session 2, Placebo Session 1, Placebo Session 2
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	4 weeks
Adverse Event Reporting Description	Participants reported adverse events to nurse at each study visit, based on a list of known adverse events and novel adverse events were also recorded.
Arm/Group Title	Placebo Session1, Aprepitant Session 2		Placebo Session1, Placebo Session 2
Arm/Group Description	Placebo in session 1; Aprepitant: 80 mg in session 2, oral administration		Placebo, one per session, oral administration
All Cause Mortality
	Placebo Session1, Aprepitant Session 2		Placebo Session1, Placebo Session 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/3 (0%)
Serious Adverse Events
	Placebo Session1, Aprepitant Session 2		Placebo Session1, Placebo Session 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Session1, Aprepitant Session 2		Placebo Session1, Placebo Session 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

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.