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Alcohol Use DisorderKMENCT03878225

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

A study testing H.V.M.N. Ketone Ester in people with Alcohol Use Disorder and Alcohol Withdrawal, run by Anders Fink-Jensen, MD, DMSci at 2 sites in Denmark.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Alcohol Use Disorder, Alcohol Withdrawal, Ketosis
What is being tested?
H.V.M.N. Ketone Ester
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
36 participants
Where
2 sitesDenmark
Study dates
15 Jun 2020to 31 Mar 2022
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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.
  • Following a low-carbohydrate diet, intermittent fasting diet or consuming nutritional ketone supplements.
  • Other substance use dependency than alcohol and/or nicotine and/or cannabis within the previous 1 month.
  • Benzodiazepine dependence within the previous 1 month and/or use of benzodiazepines within the previous 14 days.
  • Females of childbearing potential who are pregnant, breast-feeding or have intention of becoming pregnant within the next 4 months, or are not using contraceptives (during the whole study period) considered as highly effective (combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) intrauterine device - IUD, IUS, bilateral tubal occlusion, vasectomized partner, sexual abstinence) (HMA - Clinical Trials Facilitation and Coordination Group, 2014).
  • Participated in a clinical trial with investigational medication or weight reduction within the previous three months.
  • Use of Disulfiram (Antabus) in the previous 14 days prior to any planned KME ingestion or MRS procedure.
  • For HD and LD groups in MRS sub-study only: Inability to abstain from alcohol for 24 hours, to reduce risks and to avoid confounding results with alcohol withdrawal.
  • For HD and LD in MRS sub-study only: History of alcohol use disorder or alcohol withdrawal symptoms requiring medication
  • For participants undergoing MRS (all HD, LD, and LTS, some KME patients): Implanted metallic devices or objects that could potentially prove harmful when exposed to the MRS environment or procedures. Patients in the alcohol withdrawal group can still participate in the KME study if meeting this criterion, but cannot undergo subsequent MRS.
  • Any condition that the investigator estimates would interfere with trial participation and/or the safety of the participant.

Trial locations and contacts

2 sites in 1 country.

Anders Fink-Jensen, MD, DMSc contact

0045-22755843

Anders.Fink-Jensen@regionh.dk

Denmark2 sites, 2 recruiting
  • Psychiatric Center Copenhagen, Rigshospitalet

    Copenhagen, 2100

    Anders Fink-Jensen, Professor, Dmsc,, 0045-22755843, anders.fink-jensen@regionh.dk

    Jakob Damsgaard, M. D., 0045-60852901, jakob.damsgaard.01@regionh.dk

    Not yet recruiting
  • Novavi Lyngby

    Lyngby, Danmark (DK), 2800

    Jakob Damsgaard, MD, 0045-60852901, jakob.damsgaard.01@regionh.dk

    Anders Fink-Jensen, MD, DMSc, Professor, 0045-22755843, anders.fink-jensen@regionh.dk

    Recruiting

Other trials in Denmark

About this study

Official title: The Ketone Mono Ester Study - Does a Ketogenic Dietary Supplement Reduce Alcohol Withdrawal Symptoms in Humans

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:

Read more

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.

Read the 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.

Being tested
H.V.M.N. Ketone Ester, Placebo
Medical subject headings
Alcoholism, Ketosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • H.V.M.N. Ketone EsterDietary supplement

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

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

  • PlaceboOther

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

Study groups in NCT03878225
Study groupRoleWhat they receive
Ketone Mono EsterActive comparatorThe 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.
Receives: Dietary Supplement: H.V.M.N. Ketone Ester
PlaceboPlacebo comparatorThe 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.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Benzodiazepine use

    Quantity of benzodiazepine needed to manage alcohol withdrawal symptoms.

    Measured: 2 years

  2. 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.

    Measured: 2 years

Secondary outcomes (6)
  1. Sleep quality

    Daily self-reported sleep quality on a VAS scale. Self-reported estimated sleep-time in previous 24 hours.

    Measured: 2 years

  2. Alcohol withdrawal symptoms.

    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.

    Measured: 2 years

  3. Anxiety

    Anxiety assessed with VAS questionnaires

    Measured: 2 years

  4. Alcohol craving

    Alcohol craving assessed with the Desire for Alcohol Questionnaire (DAQ)

    Measured: 2 years

  5. Alcohol intake

    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

    Measured: 2 years

  6. Mood

    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.

    Measured: Assess mood measured by VAS questionnaires during the trial, and by the Major Depressive Inventory (MDI) at screening and one-month follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2019
  2. Study start15 Jun 2020
  3. Primary completion31 Dec 2021 (estimated)
  4. Study completion31 Mar 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Double blinded, randomized, placebo controlled
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03878225
Sponsor's protocol ID
H-18045204
Acronym
KME
Status last verified
Jul 2020
First submitted
13 Feb 2019
Last updated
7 Jul 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33410985

Questions about this trial

What is this clinical trial studying?

A study testing H.V.M.N. Ketone Ester in people with Alcohol Use Disorder and Alcohol Withdrawal, run by Anders Fink-Jensen, MD, DMSci at 2 sites in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 7 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Anders Fink-Jensen, MD, DMSc (0045-22755843, Anders.Fink-Jensen@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Benzodiazepine use (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03878225, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2020.

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