Trial Outcomes & Findings for Ketogenic Diet (KD) in Alcoholism (NCT NCT03255031)
NCT ID: NCT03255031
Last Updated: 2024-07-17
Results Overview
Alcohol withdrawal symptoms were measured using the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar). The CIWA-Ar is a 10-item scale scored from 0-7, with the exception of the orientation category, scored from 0-4, used in the assessment and management of alcohol withdrawal. Score ranges from 0 - 67. Mild alcohol withdrawal is defined with a score less than or equal to 10, moderate with scores 11 to 15, and severe with any score equal to or greater than 16. Analysis was performed as ANOVA between-groups.
COMPLETED
NA
53 participants
Week 1
2024-07-17
Participant Flow
Participant milestones
| Measure |
Ketogenic Diet (KD)
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
Standard American (SA) Diet
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
|---|---|---|
|
Overall Study
STARTED
|
33
|
20
|
|
Overall Study
COMPLETED
|
17
|
13
|
|
Overall Study
NOT COMPLETED
|
16
|
7
|
Reasons for withdrawal
| Measure |
Ketogenic Diet (KD)
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
Standard American (SA) Diet
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
|---|---|---|
|
Overall Study
Adverse Event
|
5
|
3
|
|
Overall Study
Physician Decision
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
9
|
3
|
Baseline Characteristics
Ketogenic Diet (KD) in Alcoholism
Baseline characteristics by cohort
| Measure |
Ketogenic Diet (KD)
n=33 Participants
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
Standard American (SA) Diet
n=20 Participants
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
Total
n=53 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
33 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
30 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
14 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
33 participants
n=5 Participants
|
20 participants
n=7 Participants
|
53 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 1Population: The analyses included participants who completed the dietary intervention.
Alcohol withdrawal symptoms were measured using the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar). The CIWA-Ar is a 10-item scale scored from 0-7, with the exception of the orientation category, scored from 0-4, used in the assessment and management of alcohol withdrawal. Score ranges from 0 - 67. Mild alcohol withdrawal is defined with a score less than or equal to 10, moderate with scores 11 to 15, and severe with any score equal to or greater than 16. Analysis was performed as ANOVA between-groups.
Outcome measures
| Measure |
Standard American (SA) Diet
n=14 Participants
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
Ketogenic Diet (KD)
n=19 Participants
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
|---|---|---|
|
Withdrawal Symptoms Measured Using the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar)
|
6.57 score on a scale
Standard Deviation 5.345
|
4.16 score on a scale
Standard Deviation 3.962
|
PRIMARY outcome
Timeframe: Week 1Population: The analyses included participants who completed the dietary intervention.
Participants received oral benzodiazepine treatment for alcohol withdrawal when Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores were 8 or higher within the first week of inpatient admission. The effect of alcohol withdrawal and benzodiazepine use was analyzed with ANOVA as the group × time effect on benzodiazepine use.
Outcome measures
| Measure |
Standard American (SA) Diet
n=14 Participants
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
Ketogenic Diet (KD)
n=19 Participants
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
|---|---|---|
|
Quantification of Medications for Control of Withdrawal Symptoms
|
156.43 mg
Standard Deviation 206.234
|
34.21 mg
Standard Deviation 79.395
|
PRIMARY outcome
Timeframe: Weeks 1, 2, and 3Population: The analyses included participants who completed the dietary intervention and had fMRI testing.
Brain network segregation was measured by functional MRI (fMRI) using the Power-264 brain atlas. The 264 spherical is defined as brain regions of interest (ROIs) with a 5-mm radius that belong to 13 large-scale functional brain networks. The fronto-parietal, ventral attention, dorsal attention, cingulo-opercular, and salience networks were grouped into the association network. The sensory hand, sensory mouth, visual, and auditory networks were grouped into the sensorimotor network. The mean time series across voxels was extracted for each regions of interest. Then the Pearson correlation coefficients was calculated between the ROIs and converted to Fisher-Z values for further analysis. Segregation equals the relative strength of within-network connectivity (Zw) when compared with between-network connectivity (Zb): Zw - Zb / Zw. Higher segregation value corelates with better functional specificity and energy efficiency. The final segregation output is a ratio of Z-scores.
Outcome measures
| Measure |
Standard American (SA) Diet
n=13 Participants
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
Ketogenic Diet (KD)
n=17 Participants
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
|---|---|---|
|
Brain Functions During Resting State: Sensorimotor Brain Network
Week 1
|
0.4816 Ratio
Standard Deviation 0.0844
|
0.5314 Ratio
Standard Deviation 0.0681
|
|
Brain Functions During Resting State: Sensorimotor Brain Network
Week 2
|
0.5028 Ratio
Standard Deviation 0.3346
|
0.5067 Ratio
Standard Deviation 0.0496
|
|
Brain Functions During Resting State: Sensorimotor Brain Network
Week 3
|
0.4849 Ratio
Standard Deviation 0.0749
|
0.4932 Ratio
Standard Deviation 0.0671
|
PRIMARY outcome
Timeframe: Weeks 1, 2, and 3Population: The analyses included participants who completed the dietary intervention and had fMRI testing.
Brain network segregation was measured by functional MRI (fMRI) using the Power-264 brain atlas. The 264 spherical is defined as brain regions of interest (ROIs) with a 5-mm radius that belong to 13 large-scale functional brain networks. The fronto-parietal, ventral attention, dorsal attention, cingulo-opercular, and salience networks were grouped into the association network. The sensory hand, sensory mouth, visual, and auditory networks were grouped into the sensorimotor network. The mean time series across voxels was extracted for each regions of interest. Then the Pearson correlation coefficients was calculated between the ROIs and converted to Fisher-z values for further analysis. Segregation equals relative strength of within-network connectivity when compared with between-network connectivity: Zw - Zb / Zw. Higher segregation value corelates with better functional specificity and energy efficiency. The final segregation output is a ratio of Z-scores.
Outcome measures
| Measure |
Standard American (SA) Diet
n=13 Participants
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
Ketogenic Diet (KD)
n=17 Participants
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
|---|---|---|
|
Brain Functions During Resting State: Association Brain Network
Week 1
|
0.3125 Ratio
Standard Deviation 0.0591
|
0.3647 Ratio
Standard Deviation 0.0537
|
|
Brain Functions During Resting State: Association Brain Network
Week 2
|
0.3346 Ratio
Standard Deviation 0.0734
|
0.3624 Ratio
Standard Deviation 0.0445
|
|
Brain Functions During Resting State: Association Brain Network
Week 3
|
0.3206 Ratio
Standard Deviation 0.06657
|
0.3563 Ratio
Standard Deviation 0.0574
|
PRIMARY outcome
Timeframe: Weeks 1, 2, and 3Population: The analyses included participants who completed the dietary intervention and the fMRI tests.
Participants performed an alcohol cue-reactivity paradigm with functional magnetic resonance imaging in which they viewed alcohol and food pictorial cues. The blood-oxygen-level dependent (BOLD) responses to food and alcohol cues was extracted and quantified the degree to which each set of brain images shared a pattern of activation using the Neurobiological Craving Signature (NCS). The NCS is a whole-brain pattern of responses to cues, with prominent regions including ventromedial prefrontal and cingulate cortices, ventral striatum, temporal/parietal association areas, mediodorsal thalamus and cerebellum. A group-by-time repeated measures ANOVA was used to test for differences in craving signature expression between the dietary groups. Positive values indicate stronger brain BOLD responses to alcohol related cues.
Outcome measures
| Measure |
Standard American (SA) Diet
n=14 Participants
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
Ketogenic Diet (KD)
n=19 Participants
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
|---|---|---|
|
Neurobiological Craving Signature (NCS) for Alcohol > Food Pictorial Cues
Week 1
|
.55 arbitrary units (A.U)
Standard Deviation 4.2818982698951
|
-2.13 arbitrary units (A.U)
Standard Deviation 3.6952873396632
|
|
Neurobiological Craving Signature (NCS) for Alcohol > Food Pictorial Cues
Week 2
|
-.67 arbitrary units (A.U)
Standard Deviation 3.5104963867952
|
-2.38 arbitrary units (A.U)
Standard Deviation 4.2621609031125
|
|
Neurobiological Craving Signature (NCS) for Alcohol > Food Pictorial Cues
Week 3
|
-.099 arbitrary units (A.U)
Standard Deviation 5.8017946230225
|
-1.37 arbitrary units (A.U)
Standard Deviation 3.2654308575651
|
PRIMARY outcome
Timeframe: Weeks 1, 2, and 3Population: The analyses included participants who completed the dietary intervention and the MRS exam.
The brain metabolism was measured with weekly magnetic resonance spectroscopy (MRS) scans in a voxel in the dorsal anterior cingulate cortex. The concentrations of Glutamate/Creatine were analyzed with repeated-measures ANOVAs with time as the within-subject factor and diet as the between-subject factor.
Outcome measures
| Measure |
Standard American (SA) Diet
n=14 Participants
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
Ketogenic Diet (KD)
n=19 Participants
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
|---|---|---|
|
Brain Concentrations of Glutamate/Creatine
Week 1
|
1.1966429 Ratio
Standard Deviation .15106015
|
1.1980558 Ratio
Standard Deviation .13154360
|
|
Brain Concentrations of Glutamate/Creatine
Week 2
|
1.20654 Ratio
Standard Deviation .103377
|
1.34895 Ratio
Standard Deviation .214281
|
|
Brain Concentrations of Glutamate/Creatine
Week 3
|
1.18600 Ratio
Standard Deviation .164481
|
1.31244 Ratio
Standard Deviation .169988
|
PRIMARY outcome
Timeframe: Weeks 1 and 3Population: The analyses included participants who completed the dietary intervention and MRI exams.
Whole brain total intracranial volume was measured using T1 structural MRI. Voxel-based morphometry (VBM) was performed using the Computational Anatomy Toolbox (CAT12) in Statistical Parametric Mapping software (SPM12).
Outcome measures
| Measure |
Standard American (SA) Diet
n=12 Participants
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
Ketogenic Diet (KD)
n=18 Participants
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
|---|---|---|
|
Brain Volume Measured With Brain MRI
Week 1
|
1462.667 cm^3
Standard Deviation 143.786
|
1482.111 cm^3
Standard Deviation 158.8806
|
|
Brain Volume Measured With Brain MRI
Week 3
|
1463.75 cm^3
Standard Deviation 147.00
|
1481.0 cm^3
Standard Deviation 161.053
|
SECONDARY outcome
Timeframe: Weeks 1, 2, and 3Population: The analyses included participants who completed the dietary intervention and the MADRS scale.
The effect of ketogenic diet on mood was assessed with the Montgomery-Asberg Depression Rating Scale (MADRS). MADRS is a ten-item diagnostic questionnaire which measures the severity of depressive episodes. Each item is rated on a score of 0 (normal/not present) to 6 (extreme symptom). Total score range is zero (0) to 60. Total score of 7-19 represent mild depression; 20-34 moderate; 35-60 indicate severe depression. Higher MADRS score indicates more severe depression/lower mood. Analysis was performed as mixed ANOVAs with group as between-group factor and time as within-subjects factor.
Outcome measures
| Measure |
Standard American (SA) Diet
n=14 Participants
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
Ketogenic Diet (KD)
n=19 Participants
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
|---|---|---|
|
Effect of Ketogenic Diet on Mood
Week 1
|
21.71 score on a scale
Standard Deviation 12.086
|
18.22 score on a scale
Standard Deviation 8.968
|
|
Effect of Ketogenic Diet on Mood
Week 2
|
7.29 score on a scale
Standard Deviation 3.872
|
6.39 score on a scale
Standard Deviation 7.632
|
|
Effect of Ketogenic Diet on Mood
Week 3
|
6.36 score on a scale
Standard Deviation 6.902
|
6.26 score on a scale
Standard Deviation 6.297
|
SECONDARY outcome
Timeframe: Weeks 1, 2, and 3Population: The analyses included participants who completed the dietary intervention and reported sleep data.
Participants self-reported their estimated total sleep time for each night. Weekly responses were reported as the average across seven days.
Outcome measures
| Measure |
Standard American (SA) Diet
n=14 Participants
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
Ketogenic Diet (KD)
n=19 Participants
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
|---|---|---|
|
Effect of Ketogenic Diet on Sleep
Week 1
|
6.0624149660000 Hours
Standard Deviation 1.0478988048910
|
5.6451754385263 Hours
Standard Deviation 1.0673525108302
|
|
Effect of Ketogenic Diet on Sleep
Week 2
|
6.1456632652857 Hours
Standard Deviation 1.0118081840508
|
5.7086466163684 Hours
Standard Deviation .75371098816986
|
|
Effect of Ketogenic Diet on Sleep
Week 3
|
6.5103741495714 Hours
Standard Deviation .78393883493517
|
5.6344611528421 Hours
Standard Deviation .87434796211452
|
SECONDARY outcome
Timeframe: Weeks 1, 2, and 3Population: The analyses included participants who completed the dietary intervention and completed the DAQ. Two participants from week 3 had missing data.
Participants rated their alcohol craving on the Desire for Alcohol Questionnaire (DAQ) weekly. DAQ is a 14-item scale that assesses current self-reported levels of alcohol craving. Each item is scored from 0 (fully disagree) to 6 (fully agree), with a total score range of zero (0) to maximum score of 84. Higher score indicates higher level of alcohol craving. Analysis was performed as repeated-measure ANOVA.
Outcome measures
| Measure |
Standard American (SA) Diet
n=14 Participants
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
Ketogenic Diet (KD)
n=19 Participants
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
|---|---|---|
|
Effect of Ketogenic Diet on Alcohol Craving
Week 1
|
21.07 score on a scale
Standard Deviation 16.041
|
22.00 score on a scale
Standard Deviation 16.327
|
|
Effect of Ketogenic Diet on Alcohol Craving
Week 2
|
20.36 score on a scale
Standard Deviation 16.402
|
17.53 score on a scale
Standard Deviation 11.649
|
|
Effect of Ketogenic Diet on Alcohol Craving
Week 3
|
18.36 score on a scale
Standard Deviation 11.098
|
15.88 score on a scale
Standard Deviation 10.511
|
Adverse Events
Ketogenic Diet (KD)
Standard American (SA) Diet
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ketogenic Diet (KD)
n=33 participants at risk
Subjects with alcohol use disorder receive ketogenic diet (KD) which consists of food, snacks, and shakes three times per day (high in fat) for up to four weeks while inpatient.
|
Standard American (SA) Diet
n=20 participants at risk
Subjects with alcohol use disorder receive Standard American (SA) diet which consists of ketogenic diet (KD) food, snacks, and shakes three times per day (high in fat) in the proportions of carbohydrates, protein and fat of traditional western diet for up to four weeks while inpatient.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/33 • Up to 4 weeks while inpatient
|
5.0%
1/20 • Up to 4 weeks while inpatient
|
|
Gastrointestinal disorders
Nausea
|
3.0%
1/33 • Up to 4 weeks while inpatient
|
0.00%
0/20 • Up to 4 weeks while inpatient
|
|
Injury, poisoning and procedural complications
Foreign body
|
3.0%
1/33 • Up to 4 weeks while inpatient
|
0.00%
0/20 • Up to 4 weeks while inpatient
|
|
Investigations
Liver function test increased
|
3.0%
1/33 • Up to 4 weeks while inpatient
|
5.0%
1/20 • Up to 4 weeks while inpatient
|
|
Nervous system disorders
Dizziness
|
3.0%
1/33 • Up to 4 weeks while inpatient
|
0.00%
0/20 • Up to 4 weeks while inpatient
|
|
Psychiatric disorders
Panic attack
|
3.0%
1/33 • Up to 4 weeks while inpatient
|
0.00%
0/20 • Up to 4 weeks while inpatient
|
|
Renal and urinary disorders
Nephrolithiasis
|
3.0%
1/33 • Up to 4 weeks while inpatient
|
0.00%
0/20 • Up to 4 weeks while inpatient
|
Additional Information
Dr. Gene-Jack Wang
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place