Does a Ketogenic Dietary Supplement Reduce Alcohol Withdrawal Symptoms in Humans?
- Conditions
- Alcohol WithdrawalKetosisAlcohol Use Disorder
- Interventions
- Dietary Supplement: H.V.M.N. Ketone EsterOther: Placebo
- Registration Number
- NCT03878225
- Lead Sponsor
- Anders Fink-Jensen, MD, DMSci
- Brief Summary
A ketogenic diet (KD) is high in fat and low in carbohydrates and induces ketosis. KD is an approved non-pharmacological therapy for drug-resistant child epilepsy. Research has shown that a KD can reduce the behavioral measures of alcohol withdrawal symptomatology in rats. Ketosis is also possible to achieve without adherence to a KD, by ingestion of a ketogenic dietary supplement. In this study, we want to investigate if the attenuating effect of the KD observed in rodents, is also applicable in humans, i.e. whether a ketogenic dietary supplement, here a ketone monoester, would be effective in suppressing alcohol withdrawal symptoms in humans.
Objective:
To test the effect of a ketogenic dietary supplement on the need for benzodiazepines in managing alcohol withdrawal syndrome in humans.
Eligibility:
Adults 18-70 years who are alcohol dependent and are seeking treatment for alcohol withdrawal syndrome in an out-patient setting.
Design:
Double blinded, randomized clinical trial. The participants will be randomized to receive either the ketone ester beverage, or a placebo beverage.
The study will be conducted over three days (72 hours), with follow-up at 1 month and 1 year after completion. A sub-set of patients will undergo Magnetic Resonance Spectroscopy (MRS) following withdrawal treatment, and again after 1 month.
- Detailed Description
Neuroimaging studies have shown that acute alcohol administration decreases glucose metabolism in the human brain, which was initially thought to reflect decreased brain function. However, subsequent studies showed that even low doses of alcohol, with minimal behavioral effects, also decreased baseline brain glucose metabolism and further. This led to the hypothesis that the reduction in brain glucose metabolism during alcohol intoxication reflected the brain's utilization of an alternate energy substrate, e.g. the alcohol metabolite acetate. Acetate is not a ketone body, but biochemically similar to the ketone bodies, which include acetoacetate, BHB and acetone. Ketone bodies are similarly taken up by the Monocarboxylate Transporters in neurons, and other brain tissue. A pre-clinical trial has demonstrated that the implementation of a KD for 10 days significantly reduced the behavioral measures of alcohol withdrawal symptomatology in rats. In this study, we want to investigate if the attenuating effect of the KD observed in rodents, is also applicable in humans, i.e. whether a ketogenic dietary supplement, here a ketone monoester, would be effective in suppressing alcohol withdrawal symptoms in humans.
Objectives:
We will investigate the effect of a five times daily oral administration of a ketone dietary supplement beverage vs. placebo on the need for benzodiazepines in alcohol withdrawal syndrome. The KME beverage is a supplement to standardized out-patient alcohol withdrawal treatment.
Study population:
36 participants aged 18-70 with a diagnosis of alcohol use disorder according to the DSM-V, ICD-10, and a previous history of treatment-requiring alcohol withdrawal syndrome.
Design:
Clinical double-blinded, randomized, placebo-controlled, three-day clinical trial, with an MRS (Magnetic Resonance Spectroscopy) sub-study. The participants will be randomized to receive either the ketone ester beverage, or a placebo beverage 5 times daily. Participants will be asked to register benzodiazepine use in a medication-diary during the study. Participants will be asked to self-monitor blood-glucose and ketone levels by use of fingerstick measurements. During the study patients will be evaluated for withdrawal severity, and complete questionnaires on alcohol craving, sleep, anxiety and mood.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 36
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ketone Mono Ester H.V.M.N. Ketone Ester The ketone mono ester is commercially available dietary supplement beverage named "H.V.M.N. Ketone Ester", marketed by HVMN Inc®. The KME beverage consists of water, D-β-hydroxybutyrate ester, stevia leaf extract, natural flavors, malic acid, potassium sorbate and potassium benzoate. The active ingredient is the D-β-hydroxybutyrate ester, with each dose containing 25g. Participants will be asked to ingest this 5 times daily for 3 days (72 hours), to a total of 15 doses during the study. Placebo Placebo The placebo beverage will consist of water added with a colorless, bitter flavor enhancer and a sweetening agent (Stevia) to approximate the taste of the KME beverage as closely as possible. The bitter flavor enhancer used is denatonium benzoate (Bitrex®). The placebo beverage will be delivered to patients in bottles identical to those used in the active arm. Patients, investigators and other caregivers will be blinded to treatment allocation until time of database unlock.
- Primary Outcome Measures
Name Time Method Benzodiazepine use 2 years Quantity of benzodiazepine needed to manage alcohol withdrawal symptoms.
Magnetic Resonance Spectroscopy sub-study 2 years For the MRS sub-study brain BHB, GABA and Glutamate will be measured with 1H MRS following KME ingestion. Results will be compared with healthy volunteers with differing alcohol consumption habits.
- Secondary Outcome Measures
Name Time Method Sleep quality 2 years Daily self-reported sleep quality on a VAS scale. Self-reported estimated sleep-time in previous 24 hours.
Alcohol withdrawal symptoms. 2 years Alcohol withdrawal symptoms assessed by use of the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). Measures of pulse, blood pressure and respiratory frequency.
Alcohol craving 2 years Alcohol craving assessed with the Desire for Alcohol Questionnaire (DAQ)
Alcohol intake 2 years Asses alcohol intake after the trial at one month and one year after completion, using the Timeline Follow Back method (TLFB). Assess the Alcohol Use Disorder Identification Test (AUDIT) at the beginning of the trial and one year after termination of the trial
Mood Assess mood measured by VAS questionnaires during the trial, and by the Major Depressive Inventory (MDI) at screening and one-month follow-up Mood, assessed by the Major Depression Inventory scale, MDI. The MDI is a self report mood questionnaire. Symptoms are rated based on how the patient has been feeling over the past two weeks.
The diagnostic demarcation line indicates at which point a symptom is severe enough to be used in the DSM-IV diagnostic algorithm of major depression.
Each question has a point giving system from 0-5 points. The higher the score, the more severe outcome. Scores from 20-24 indicates minor depressive symptoms. Scores from 25-29 indicates a moderate depression. Scores from 30 and above indicates major depressive symptoms.Anxiety 2 years Anxiety assessed with VAS questionnaires
Trial Locations
- Locations (2)
Novavi Lyngby
🇩🇰Lyngby, Danmark (DK), Denmark
Psychiatric Center Copenhagen, Rigshospitalet
🇩🇰Copenhagen, Denmark