Does a Ketogenic Dietary Supplement Reduce Alcohol Withdrawal Symptoms in Humans?

NCT03878225 | Unknown

• 1 other identifier: H-18045204
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

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.

Conditions

Alcohol Use Disorder; Alcohol Withdrawal; Ketosis

Outcome Measures

Primary Outcomes (2)

• Benzodiazepine use

  Quantity of benzodiazepine needed to manage alcohol withdrawal symptoms.

  2 years

• Magnetic Resonance Spectroscopy sub-study

  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.

  2 years

Secondary Outcomes (6)

• Sleep quality

  2 years

• Alcohol withdrawal symptoms.

  2 years

• Anxiety

  2 years

• Alcohol craving

  2 years

• Alcohol intake

  2 years

Study Arms (2)

Ketone Mono Ester

ACTIVE COMPARATOR

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.

Dietary Supplement: H.V.M.N. Ketone Ester

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

H.V.M.N. Ketone Ester DIETARY_SUPPLEMENT

The ketone mono ester will be ingested 5 times daily for 3 days (72 hours). Please see above for details.

Also known as: Ketone beverage, ketone mono ester (https://hvmn.com/ketone)

Ketone Mono Ester

Placebo OTHER

The placebo will be ingested 5 times daily for 3 days (72 hours). Please see above for details.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 18 and 70 years of age.
• Ability to provide written informed consent as determined by the physical examination and verbal communication. The capacity to consent will be determined by study personnel.
• Alcohol-dependent individuals must meet alcohol dependency syndrome criteria according to ICD-10 and alcohol use disorder according to DSM-5, have a score \>15 on the Alcohol Use Disorder Identification Test (AUDIT) and a history of previous treatment for alcohol withdrawal syndrome following cessation of alcohol use.
• Between 18 and 70 years of age.
• Ability to provide written informed consent as determined by the physical examination and verbal communication. The capacity to consent will be determined by study personnel.
• Light drinkers (LD): Alcohol consumption less than 7 drinks per week typically over the past year and no more than three drinks per occasion. AUDIT score below 7 in the Alcohol Use Disorder Identification Test.
• Heavy drinkers (HD): Not treatment-seeking and not fulfilling criteria for alcohol dependence syndrome according to ICD-10 or alcohol use disorder according to DSM-5. For at least one-year consuming alcohol at a typical rate of above a level of 14 drinks per week for men and consume at least 4 drinks per day at least once per week. For females, consume alcohol in excess of 11 drinks per week and exceed 3 drinks per day at least once per week.
• Long term sober (LTS): For the long-term sober group, a previous diagnosis of alcohol dependence, consumed no alcohol in the previous 6 months.

You may not qualify if:

• Diagnosis of current psychiatric disorder that is deemed not stable by the study physician, except for the following:
• Diagnosis of nicotine dependence
• Alcohol withdrawal patients may have a diagnosis of alcohol dependence
• HD may have a diagnosis of alcohol abuse
• Lifetime diagnosis of bipolar disorder, schizophrenia, paranoid psychosis or mental retardation.
• Incapable of understanding and/or speaking Danish.
• Head trauma with loss of consciousness for more than 60 minutes (self-report, medical history).
• Lifetime diagnosis of epilepsy.
• Alcohol withdrawal seizures within the previous 3 months.
• Use of any medication that could interfere with study assessments, including anticonvulsants, benzodiazepines and non-benzodiazepine hypnotics (Zopiclone and/or Zolpidem). Use of medications will be reviewed by a study physician on a case by case basis.
• Body Mass Index, BMI, \< 18.5 kg/m2 or body weight \<60 kg or \>120kg.
• Urine positive for cocaine, amphetamines, methadone, opioids or benzodiazepines.
• Blood glucose \>12.2 mmol/L on finger-prick measurement (\>7.0 if over-night fasted).
• Known kidney disease, pancreatic disease, porphyria or other mitochondrial diseases, type 1 diabetes, type 2 diabetes or any other history of severe somatic illness that the investigator believes would interfere with trial participation.
• Known cirrhosis or clinical evidence of significant liver disease, such as ascites or hepatosplenomegaly.

Sponsors & Collaborators

• Anders Fink-Jensen, MD, DMSci: lead

Study Sites (2)

Novavi Lyngby

Lyngby, Danmark (DK), 2800, Denmark

RECRUITING

Psychiatric Center Copenhagen, Rigshospitalet

Copenhagen, 2100, Denmark

NOT YET RECRUITING

Related Publications (1)

• Bornebusch AB, Mason GF, Tonetto S, Damsgaard J, Gjedde A, Fink-Jensen A, Thomsen M. Effects of ketogenic diet and ketone monoester supplement on acute alcohol withdrawal symptoms in male mice. Psychopharmacology (Berl). 2021 Mar;238(3):833-844. doi: 10.1007/s00213-020-05735-1. Epub 2021 Jan 7.

  PMID: 33410985 DERIVED

MeSH Terms

Conditions

Alcoholism; Ketosis

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Anders Fink-Jensen, MD, DMSc

  Psychiatric Center Copenhagen, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anders Fink-Jensen, MD, DMSc

CONTACT

0045-22755843; Anders.Fink-Jensen@regionh.dk

Jakob Damsgaard, MD

CONTACT

0045-60852901; jakob.damsgaard.01@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Randomization will be stratified according to gender and body-weight. The randomization uses stratified permuted block randomization. Selected un-blinded personnel will carry out the randomization procedure. After randomization is carried out, the ketone mono ester or placebo beverages will be delivered to the patients by blinded personnel. Patients, investigators, other caregivers and persons performing data analysis will remain blinded from the time of randomization until the time of database unlock. Un-blinded project personnel will prepare and pack the ketone mono ester/placebo beverage in identical bottles. The placebo beverage will consist of water added with a colorless, bitter flavor enhancer (Bitrex®) and a sweetening agent (Stevia) to approximate the taste of the ketone mono ester beverage as closely as possible.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Dmsc,

Model Details: Double blinded, randomized, placebo controlled

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: March 18, 2019
• Study Start: June 15, 2020
• Primary Completion: December 31, 2021
• Study Completion: March 31, 2022
• Last Updated: July 7, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)