NCT03132233

Brief Summary

Approx. one billion people are suffering from migraine worldwide and yet, therapeutic options are still very limited. Research suggests that changes in energy metabolism could be part of migraine pathophysiology. Ketone bodies (KB) are endogenous alternative energy substrates. Our clinical trial assesses the efficacy and safety of KB supplements in 60-90 adult migraineurs (5-14 migraine days / months) at the University Hospital Basel. The total duration of the trial is approx. 6 months, consisting of 4 weeks baseline, 12 weeks intervention with KB powder or matched placebo and 8 weeks follow-up. The primary endpoint is the change in migraine days at the end of intervention compared to baseline. Additionally, changes in gene expression, fat-, and glucose metabolism, inflammatory markers and quality of life will be examined.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started May 2017

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 11, 2017

Completed
16 days until next milestone

First Posted

Study publicly available on registry

April 27, 2017

Completed
11 days until next milestone

Study Start

First participant enrolled

May 8, 2017

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 16, 2020

Completed
15 days until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2020

Completed
Last Updated

March 27, 2020

Status Verified

March 1, 2020

Enrollment Period

2.7 years

First QC Date

April 11, 2017

Last Update Submit

March 26, 2020

Conditions

MigraineEpisodic Migraine

Keywords

MigrainePreventionProphylaxisKetone bodiesBeta-hydroxybutyrateDouble-blindRandomisedPlacebo controlledMitochondrial functioningEnergy metabolismInterventionDietary Supplement

Outcome Measures

Primary Outcomes (1)

  • Number of migraine days

    Mean change from baseline in number of migraine days (meeting International Classification of Headache Disorders (ICHD)-3 criteria) during the last month of intervention in treatment group compared to placebo.

    Last 4 weeks of intervention compared to baseline 4 weeks.

Secondary Outcomes (5)

  • Number of headache days

    Last 4 weeks of intervention compared to baseline 4 weeks.

  • Acute migraine medication

    Last 4 weeks of intervention compared to baseline 4 weeks.

  • Migraine intensity

    Last 4 weeks of intervention compared to baseline 4 weeks.

  • Migraine Disability Assessment (MIDAS)

    Last 4 weeks of intervention compared to baseline 4 weeks.

  • Headache Impact Test (HIT)

    Last 4 weeks of intervention compared to baseline 4 weeks.

Other Outcomes (1)

  • Exploratory biomarker assessments

    Last 4 weeks of intervention compared to baseline 4 weeks.

Study Arms (2)

Verum

ACTIVE COMPARATOR

Receives the investigational medicine product (IMP; Beta-hydroxybutyrate calcium and magnesium salt).

Dietary Supplement: Beta-hydroxybutyrate calcium and magnesium salt

Placebo

PLACEBO COMPARATOR

Receives a matched placebo powder to the IMP.

Other: placebo powder

Interventions

Beta-hydroxybutyrate calcium and magnesium saltDIETARY_SUPPLEMENT

Exogenous ketone body in mineral salt form.

Verum
placebo powderOTHER

matched placebo powder to the IMP.

Placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Has been previously diagnosed with migraine (with or without aura) in accordance with the ICHD-3 Beta Classification criteria.
  • Experience between 5 and 14 migraine days per month (over the last 4 months).
  • Has age of onset of migraine less than 50 years old.
  • Agrees to refrain from initiating or changing the type, dosage or frequency of any prophylactic medications (exclusive of medications taken for acute relief of migraine symptoms) as well as dietary supplements (such as Q10, riboflavin etc) against migraine and for indications other than migraine that in the opinion of the clinician may interfere with the study objectives (e.g. antidepressant, anticonvulsants, beta blockers, etc.) for the duration of the study.
  • Has not changed type, dosage or frequency of any prophylactic medications (exclusive of medications taken for acute relief of migraine symptoms) as well as dietary supplements (such as Q10, riboflavin etc) against migraine and for indications other than migraine that in the opinion of the clinician may interfere with the study objectives (e.g. antidepressant, anticonvulsants, beta blockers, etc.) for at least 3 months prior to study onset.
  • Refrains to make any drastic changes to the diet for the duration of the study, including periods of fasting.
  • Agrees to use the study intervention as intended, follow all of the requirements of the study including follow-up visit requirements, record required study data in the subject dairy and other self-assessment questionnaires and is okay with drawing blood samples.
  • Is able to provide written Informed Consent.

You may not qualify if:

  • Has a concomitant medical condition that will require oral or injectable steroids during the study.
  • Has a history of any significant neurological, psychiatric or other medical condition that in the opinion of the investigator may confound the study assessments, liver and kidney diseases in particular.
  • Is currently treated for a thyroid disease or has a history thereof.
  • Has a cardiovascular disease (hypertension in particular) or a history thereof.
  • Has a known history of suspected secondary headache.
  • Currently takes simple analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) greater then 14 days per month or triptans greater than 10 days per month for headaches or other body pain.
  • Currently takes prescription opioids.
  • Has previous diagnosis of medication overuse headache (MoH) , which has reverted to episodic migraine within the last 6 months.
  • Meets the ICHD-3 Beta Classification criteria for chronic migraine (\> 15 headache days per month).
  • Has failed an adequate trial (two months or greater) of at least 3 classes of a drug therapy for the prophylaxis of migraine .
  • Has had surgery for migraine prevention.
  • Has received Botox injections within the last 6 months.
  • Is pregnant or thinking of becoming pregnant during the study period, or of childbearing years and is unwilling to use and accepted form of birth control.
  • Is participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days.
  • Belongs to a vulnerable population or has any condition such that his or her ability to provide informed consent, comply with the follow-up requirements, or provide self- assessments is compromised (e.g. homeless, developmentally disabled and prisoner).
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Children's Hospital (UKBB)

Basel, Canton of Basel-City, 4031, Switzerland

Location

Related Publications (5)

  • Putananickal N, Gross EC, Orsini AL, Schmidt S, Hafner P, Gocheva V, Nagy S, Henzi BC, Rubino D, Schadelin S, Sandor P, Fischer D. Metabolic markers of short and long-term exogenous DL-beta-hydroxybutyrate supplementation in episodic migraine patients: an exploratory analysis of a randomized-controlled-trial. Front Pharmacol. 2023 May 4;14:1172483. doi: 10.3389/fphar.2023.1172483. eCollection 2023.

    PMID: 37214431DERIVED

  • Gross EC, Putananickal N, Orsini AL, Schoenen J, Fischer D, Soto-Mota A. Defining metabolic migraine with a distinct subgroup of patients with suboptimal inflammatory and metabolic markers. Sci Rep. 2023 Mar 7;13(1):3787. doi: 10.1038/s41598-023-28499-y.

    PMID: 36882474DERIVED

  • Putananickal N, Gross EC, Orsini AL, Schmidt S, Hafner P, Gocheva V, Nagy S, Henzi BC, Rubino D, Vogt DR, Cichon S, Sandor P, Fischer D. Efficacy and safety of exogenous beta-hydroxybutyrate for preventive treatment in episodic migraine: A single-centred, randomised, placebo-controlled, double-blind crossover trial. Cephalalgia. 2022 Apr;42(4-5):302-311. doi: 10.1177/03331024211043792. Epub 2021 Sep 20.

    PMID: 34541914DERIVED

  • Gross EC, Putananickal N, Orsini AL, Vogt DR, Sandor PS, Schoenen J, Fischer D. Mitochondrial function and oxidative stress markers in higher-frequency episodic migraine. Sci Rep. 2021 Feb 25;11(1):4543. doi: 10.1038/s41598-021-84102-2.

    PMID: 33633187DERIVED

  • Gross E, Putananickal N, Orsini AL, Schmidt S, Vogt DR, Cichon S, Sandor P, Fischer D. Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial. Trials. 2019 Jan 17;20(1):61. doi: 10.1186/s13063-018-3120-7.

    PMID: 30654835DERIVED

Related Links

MeSH Terms

Conditions

Migraine Disorders

Condition Hierarchy (Ancestors)

Headache Disorders, PrimaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Study Officials

  • Dirk Fischer, MD

    Professor and head doctor

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Double-blind
Purpose
PREVENTION
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 11, 2017

First Posted

April 27, 2017

Study Start

May 8, 2017

Primary Completion

January 16, 2020

Study Completion

January 31, 2020

Last Updated

March 27, 2020

Record last verified: 2020-03

Data Sharing

IPD Sharing
Will not share

Locations

CH(1)