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| ID | Type | Description | Link |
|---|---|---|---|
| K23AA025399 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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This study will examine the effect of N-Acetylcysteine (NAC), an over-the-counter antioxidant supplement, on brains of youth (ages 15-19) using magnetic resonance imaging (MRI).
55 adolescents will receive, in a counterbalanced order, a 10-day course of NAC 1200 mg twice daily and a subsequent 10-day course of matched placebo twice daily, separated by 11 days. Urine and blood samples will be collected at baseline and urine samples again before and after each course of medication treatment. Participants will receive a 1- hour MRI scan at baseline and after each treatment trial.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| N-Acetylcysteine, then Placebo | Experimental | Participants first received N-Acetylcysteine 600mg capsules by mouth, two pills twice daily will be taken for 10 days. After washout for 11 days, they then received placebo capsules mimicking N-Acetylcysteine (two pills, twice daily) will be taken for 10 days. |
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| Placebo, then N-Acetylcysteine | Experimental | Participants first received placebo capsules mimicking N-Acetylcysteine (two pills, twice daily) will be taken for 10 days. After washout for 11 days, they then received N-Acetylcysteine 600mg capsules by mouth, two pills twice daily will be taken for 10 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| N-Acetylcysteine | Drug | N-Acetylcysteine; 600mg capsules by mouth, two pills twice daily (total 2400 mg/day). Participants will undergo MRI (including magnetic resonance imaging and functional MRI during an alcohol cue reactivity task) at baseline, after 10 days of N-Acetylcysteine and after 10 days of placebo. |
| Measure | Description | Time Frame |
|---|---|---|
| Quantifying the Difference in Glutamate Levels (mmol/kg) During N-Acetylcysteine Versus Placebo in the Anterior Cingulate Brain Region. | Using magnetic resonance spectroscopy and a within-subjects design, we will determine the effect of N-Acetylcysteine versus placebo on modulating anterior cingulate glutamate levels in adolescents. Values provided are absolute values (mmol/kg) at the end of each intervention period. Due to complexities of this method, "normal" levels of glutamate are not known; thus, we cannot make conclusions about the meaning of "higher" or "lower" glutamate levels when comparing N-acetylcysteine to placebo. | 31 days total (levels compared after 10 days on N-Acetylcysteine and 10-days of placebo with 11 day washout period in between) |
| Change in Neural Reactivity (as Measured by BOLD: Blood Oxygen Level-Dependent Response) in Reward Regions During Alcohol-cue Reactivity Task. | Assessing the change in neural reactivity to alcohol cues after each round of medication: Placebo vs. N-Acetylcysteine. Cue reactivity is a type of learned response which is observed in individuals who use substances (e.g., alcohol) and involves significant physiological reactions to presentations of substance-related stimuli (i.e., alcohol images) in comparison to neutral images (e.g., non-alcoholic beverages ) measured by BOLD (Blood Oxygen Level-Dependent response). ROIs were (left and right hemisphere): amygdala, caudate, insula, nucleus accumbens, and putamen. Change in BOLD signal are reported in Z-scores. A Z-score of 0 would indicate there is no statistical difference in BOLD signal between alcohol images and non-alcohol beverage images. A higher Z-score would indicated a higher BOLD signal during alcohol images compared to non-alcohol beverage images. A lower Z-score would indicate a lower BOLD signal during alcohol images compared to non-alcohol beverage images. | 31 days total (levels compared after 10 days on N-Acetylcysteine and 10-days of placebo with 11 day washout period in between) |
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Inclusion criteria: Participants were between the ages of 15-19 and may or may not have used alcohol. All participants in the alcohol-using group met criteria for heavy drinking, based on quantity and frequency of drinking (Squeglia et al. 2011; Squeglia et al. 2012) (see Figure 2).
Exclusionary criteria: Not having a parent to consent (for those under age 18); history of alcohol treatment or treatment-seeking; current DSM-5 diagnosis of moderate or severe substance use disorder other than alcohol or cannabis (American Psychiatric Association 2013); positive urine toxicology screen for narcotics, amphetamines, sedatives, hypnotics, or opiates (not prescribed by a doctor); alcohol withdrawal (> 10 on the Clinical Institute Withdrawal Assessment for Alcohol (Sullivan et al. 1989); medical conditions or medications that contraindicate taking NAC; current use of N-acetylcysteine or any supplement containing N-acetylcysteine (must agree not to take any such supplement throughout study participation); medical history of severe asthma (uncontrolled with medication); history of a serious medical, psychiatric, or neurological problem that could affect neural response, brain development, or study participation, including diabetes, seizure disorder, and severe head injury with loss of consciousness; history of learning disability, pervasive developmental disorder, or other condition requiring special education; current use of psychoactive medications that affect cerebral blood flow; non-correctable visual or hearing problems; non-fluent in English; MRI contraindications (e.g., braces, claustrophobia, irremovable metal implants or piercings); (for females) pregnancy or refusal to use reliable methods of birth control; refusal of blood draw, abstinence from alcohol for >14 days before participation, and use of alcohol <12 hours before scanning (confirmed with breathalyzer). While cigarette and marijuana use will not be exclusionary, we will exclude any participants who are daily users of cannabis or tobacco.
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| Name | Affiliation | Role |
|---|---|---|
| Lindsay M Squeglia, PhD | Medical University of South Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
35 of 57 were randomized. Of those not randomized, 12 were ineligible, 6 declined to participate, and 4 withdrew or were withdrawn during the baseline visit.
57 participants were screened for eligibility between October 16, 2017 and February 18, 2022 at the Medical University of South Carolina.
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| ID | Title | Description |
|---|---|---|
| FG000 | N-Acetylcysteine, Then Placebo | N-Acetylcysteine 600mg capsules by mouth, two pills twice daily will be taken for 10 days. After washout for 11 days, placebo capsules mimicking N-Acetylcysteine (two pills, twice daily) will be taken for 10 days. |
| FG001 | Placebo, Then N-Acetylcysteine | Placebo capsules mimicking N-Acetylcysteine (two pills, twice daily) will be taken for 10 days. After washout for 11 days, N-Acetylcysteine 600mg capsules by mouth, two pills twice daily will be taken for 10 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Before Intervention) |
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| First Intervention (10-Days) |
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| Washout Period (11-Days) |
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| Second Intervention (10-Days) |
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| ID | Title | Description |
|---|---|---|
| BG000 | N-Acetylcysteine, Then Placebo | N-Acetylcysteine 600mg capsules by mouth, two pills twice daily will be taken for 10 days. After washout for 11 days, placebo capsules mimicking N-Acetylcysteine (two pills, twice daily) will be taken for 10 days. |
| BG001 | Placebo, Then N-Acetylcysteine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Quantifying the Difference in Glutamate Levels (mmol/kg) During N-Acetylcysteine Versus Placebo in the Anterior Cingulate Brain Region. | Using magnetic resonance spectroscopy and a within-subjects design, we will determine the effect of N-Acetylcysteine versus placebo on modulating anterior cingulate glutamate levels in adolescents. Values provided are absolute values (mmol/kg) at the end of each intervention period. Due to complexities of this method, "normal" levels of glutamate are not known; thus, we cannot make conclusions about the meaning of "higher" or "lower" glutamate levels when comparing N-acetylcysteine to placebo. | Posted | Mean | Standard Deviation | mmol/kg | 31 days total (levels compared after 10 days on N-Acetylcysteine and 10-days of placebo with 11 day washout period in between) |
|
31 days (10 days of first intervention, 11-day wash out, 10 days of second intervention) Intervention = N-acetylcysteine, then Placebo OR Placebo, then N-acetylcysteine
Participants were asked about adverse events at every visit, either from a research assistant, principal investigator, medical clinician, or other study staff.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | N-Acetylcysteine | N-Acetylcysteine 600mg capsules by mouth, two pills twice daily for 10 days. N-Acetylcysteine: N-Acetylcysteine pill. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA | Systematic Assessment | Mild, causality: remote, no action taken |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lindsay M. Squeglia, PhD | Medical University of South Carolina | 843-792-5451 | squegli@musc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Detailed Protocol & General Statistical Analysis Plan | Oct 19, 2021 | May 10, 2023 | Prot_SAP_003.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Detailed SAP | Nov 30, 2022 | May 10, 2023 | SAP_004.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 19, 2021 | May 10, 2023 | ICF_005.pdf |
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| ID | Term |
|---|---|
| D000428 | Alcohol Drinking |
| ID | Term |
|---|---|
| D004327 | Drinking Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D000111 | Acetylcysteine |
| ID | Term |
|---|---|
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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|
| Placebo Oral Capsule | Drug | N-acetylcysteine-matched placebo tablet two pills twice daily. Participants will undergo MRI (including magnetic resonance imaging and functional MRI during an alcohol cue reactivity task) at baseline, after 10 days of N-Acetylcysteine and after 10 days of placebo. |
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| NOT COMPLETED |
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Placebo capsules mimicking N-Acetylcysteine (two pills, twice daily) will be taken for 10 days. After washout for 11 days, N-Acetylcysteine 600mg capsules by mouth, two pills twice daily will be taken for 10 days |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Placebo | Placebo capsules mimicking N-Acetylcysteine (two pills, twice daily) will be taken for 10 days |
|
|
|
| Primary | Change in Neural Reactivity (as Measured by BOLD: Blood Oxygen Level-Dependent Response) in Reward Regions During Alcohol-cue Reactivity Task. | Assessing the change in neural reactivity to alcohol cues after each round of medication: Placebo vs. N-Acetylcysteine. Cue reactivity is a type of learned response which is observed in individuals who use substances (e.g., alcohol) and involves significant physiological reactions to presentations of substance-related stimuli (i.e., alcohol images) in comparison to neutral images (e.g., non-alcoholic beverages ) measured by BOLD (Blood Oxygen Level-Dependent response). ROIs were (left and right hemisphere): amygdala, caudate, insula, nucleus accumbens, and putamen. Change in BOLD signal are reported in Z-scores. A Z-score of 0 would indicate there is no statistical difference in BOLD signal between alcohol images and non-alcohol beverage images. A higher Z-score would indicated a higher BOLD signal during alcohol images compared to non-alcohol beverage images. A lower Z-score would indicate a lower BOLD signal during alcohol images compared to non-alcohol beverage images. | Posted | Mean | Standard Deviation | Z-score | 31 days total (levels compared after 10 days on N-Acetylcysteine and 10-days of placebo with 11 day washout period in between) |
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|
|
|
| 0 |
| 34 |
| 0 |
| 34 |
| 10 |
| 34 |
| EG001 | Placebo Oral Capsule | Placebo capsules by mouth, two pills twice daily for 10 days. Placebo Oral Capsule: Sugar pill to mimic. | 0 | 34 | 0 | 34 | 5 | 34 |
| EG002 | Washout Period | 11-days with no medication, but check in with study staff and assessment of AEs | 0 | 33 | 0 | 33 | 1 | 33 |
| EG003 | Baseline | Prior to first intervention | 0 | 35 | 0 | 35 | 2 | 35 |
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| Headache | Nervous system disorders | MedDRA | Systematic Assessment | Mild, Definitely Not Related, No Action Taken |
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| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment | Mild, remotely related, no action taken |
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| Conjunctivitis | Eye disorders | MedDRA | Systematic Assessment | Milld, Definitely not related, Referred to/seen by PCP |
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| Skin and subcutaneous tissue disorder | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment | Mild, remotely related, no action taken |
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| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment | Mild or moderate, possibly related, no action taken |
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| Stomachache | Gastrointestinal disorders | MedDRA | Systematic Assessment | Mild, Possibly related, No action taken |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment | Mild, Definitely not related, no action taken |
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| Sore Throat | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment | Moderate, definitely not related, Referred to/seen by PCP |
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| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA | Systematic Assessment | Mild, probably related, no action taken |
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| Viral Upper Respiratory Tract Infection | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment | Mild, definitely not related, no action taken |
|
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| D000596 |
| Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| Left Caudate |
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| Right Caudate |
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| Left Insula |
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| Right Insula |
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| Left Nucleus Accumbens |
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| Right Nucleus Accumbens |
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| Left Putamen |
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| Right Putamen |
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| Superiority |