Ketamine/Placebo Family History Positive Study

NMDA Dysregulation in Individuals With a Family Vulnerability to Alcoholism

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00588952

Enrollment

Registered

2008-01-09

Start date

2001-03-31

Completion date

2015-06-30

Last updated

2021-10-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alcoholism

Brief summary

The proposed study is the first to explore the contribution of brain glutamate systems, a major target of ethanol in the brain, to the vulnerability to develop alcoholism. This study may lead to an enhanced understanding of the underlying neurobiological mechanism in high-risk individuals that may lead to the transition from moderate to excessive use of alcohol.

Detailed description

Males and females with a paternal family history of alcoholism have a high risk for developing alcoholism. These individuals have been shown to decrease dysphoric responses to alcohol self-administration that may promote the excessive use of alcohol. Ethanol has been shown to be an antagonist at the N-methyl-D-aspartate (NMDA) glutamate receptor. We have recently shown that sober alcoholics have decreased dysphoric response to the NMDA antagonist, ketamine. We propose to test the hypothesis that this characteristic exists as a vulnerability factor in those individuals susceptible to develop alcoholism. Specifically, the objective is to determine whether individuals with a family history positive (FHP) for alcoholism will experience less dysphoric, anxiogenic, and psychotogenic effects to ketamine infusion when compared to family history negative (FHN) control subjects. Male and female subjects, FHP (biological father and one other first degree relative) between the ages of 21-30, and matched controls (FHN) will complete 2 test days in a randomized balanced order under double-blind conditions. Test days will involve the 60-minute intravenous infusion of placebo and ketamine. Outcome measures include the Biphasic Alcohol Scale and visual analog scales for mood states. Secondary measures include visual analog scales for high, similarity to ethanol, the Sensation Scale (a validated measure of ethanol-like sensations) and aspects of craving for alcohol.

Interventions

DRUGKetamine and Placebo

Two test days will involve administration of placebo and Ketamine (0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute) intravenously for 60 minutes

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

DOUBLE (Subject, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

21 Years to 30 Years

Healthy volunteers

Yes

Inclusion criteria

1. Male and female between the ages of 21 and 30 years 2. Medically and neurologically healthy on the basis of history, physical examination, EKG, screening laboratories, absence of current and/or past substance abuse For Family History Positive (FHP) Subjects: Biological father and another first or second-degree biological relative with history of alcoholism

Exclusion criteria

1. Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) psychiatric and substance abuse diagnosis by history on psychiatric evaluation that includes a structured diagnostic interview (The Semi-Structured Assessment for the Genetics of alcoholism: SSAGA) and the Wisconsin Scales of Psychosis Proneness 2. History of counseling or psychotherapy; except family therapy centered around another family member 3. Extended unwillingness to remain alcohol-free for three days prior to testing and for the duration of the testing period 4. For women: positive pregnancy test at screening or intention to engage in unprotected sex during the study 5. Alcohol naïve 6. Previous bad experience with ketamine 7. Adoptee and no contact with family members For Family History Negative (FHN) Subjects: NO family history of alcoholism in any first or second-degree relatives (subjects must reliably report on three first-degree relatives)

Design outcomes

Primary

Measure	Time frame	Description
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation	Baseline	Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulation	Baseline	Self-reporting rating scale to measure the stimulation effects (0 not at all stimulated - 70 extremely stimulated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Family History Positive Subjects with a positive family history of alcoholism Ketamine and Placebo: Two test days will involve administration of placebo and Ketamine (0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute) intravenously for 60 minutes	29
Family History Negative Subjects with a negative family history of alcoholism Ketamine and Placebo: Two test days will involve administration of placebo and Ketamine (0.23 mg/kg, loading dose and infusion rate 0.58 mg/kg/minute) intravenously for 60 minutes	70
Total	99

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	2
Overall Study	Withdrawal by Subject	3	5

Baseline characteristics

Characteristic	Family History Negative	Family History Positive	Total
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	70 Participants	29 Participants	99 Participants
Age, Continuous	24.13 years STANDARD_DEVIATION 2.34	24.97 years STANDARD_DEVIATION 3.02	24.37 years STANDARD_DEVIATION 2.57
Region of Enrollment United States	70 participants	29 participants	99 participants
Sex: Female, Male Female	36 Participants	13 Participants	49 Participants
Sex: Female, Male Male	34 Participants	16 Participants	50 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 29	2 / 70
serious Total, serious adverse events	0 / 29	0 / 70

Outcome results

Primary

Biphasic Alcohol Effects Scale (BAES) - Subscale Sedation

Self-reporting rating scale to measure the sedative effects (0 not at all sedated - 70 extremely sedated) of alcohol effects. We used the BAES to measure alcohol-like effects in subjects that received ketamine infusions.

Time frame: Baseline