Clinical Trial: Energy for the Brain

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Safety, Tolerability and Efficacy of Exogenous Ketone Bodies for Preventive Treatment of Migraine: A Randomised, Placebo-controlled, Double-blind Study

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.

Detailed Summary: Migraine is a complex, common and debilitating neurological disorder. It affects approximately 17% of women and 8% of men in Europe and yet, its primary pathogenic mechanisms are still largely unknown. Various lines of research suggest that brain energy metabolism abnormalities are likely to be part of migraine pathophysiology. Specifically, there is some evidence for reversible abnormalities in mitochondrial functioning in migraine. For example, treatment with riboflavin and coenzyme Q10 has been shown to have migraine protective effects, probably via a positive effect on energy metabolism. Lactic and pyruvic acid, markers of mitochondrial (mt) disease, have been found to be increased in migraineurs; 31P-magnetic resonance spectroscopy (MRS) patterns seen in migraine are consistent with what is seen in mitochondrial disorders; cytochrome oxidase (COX)-negative fibres typical of mt diseases have also been seen in some patients with migraine. A break-down of the resting membrane potential due to lack of adenosine triphosphate (ATP) could explain cortical abnormalities in excitability, which have been reported in migraine. Despite causing a huge amount of suffering and a substantial amount of costs for society current migraine treatment options are limited. None of the prophylactic agents licensed to date are migraine-specific and most are associated with significant- sometimes intolerable- side-effects. Furthermore, their migraine-preventive properties are moderate at most. Hence, there is a need for developing alternative anti-migraine therapies. Several case studies and a first proof of concept study have demonstrated a reduction in migraine attack frequency, severity and use of acute anti-migraine medication during ketosis - with effects sizes ranging from total absence of attacks to a reduction to 1/5th of the run-in period. In addition, preliminary evidence suggests that the migraine-protective effect may outlast the duration of ketosis. This might be a result o
Sponsor: University Hospital, Basel, Switzerland

Current Primary Outcome: Number of migraine days [ Time Frame: Last 4 weeks of intervention compared to baseline 4 weeks. ]

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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of headache days [ Time Frame: Last 4 weeks of intervention compared to baseline 4 weeks. ]
    Mean change from baseline in number of headache days of any severity (meeting ICHD-3 criteria) during the last month of intervention in treatment group compared to placebo.
  • Acute migraine medication [ Time Frame: Last 4 weeks of intervention compared to baseline 4 weeks. ]
    Mean change from baseline in consumption of acute migraine medication (analgesics or triptans) measured in days with acute headache medication use during the last month of the intervention.
  • Migraine intensity [ Time Frame: Last 4 weeks of intervention compared to baseline 4 weeks. ]
    Mean change from baseline in migraine intensity (measured with a numerical rating scale from 1-10) during the last of month of the intervention period.
  • Migraine Disability Assessment (MIDAS) [ Time Frame: Last 4 weeks of intervention compared to baseline 4 weeks. ]
    Score in Migraine Disability Assessment (MIDAS; end of baseline versus end of intervention).
  • Headache Impact Test (HIT) [ Time Frame: Last 4 weeks of intervention compared to baseline 4 weeks. ]
    Score in Headache Impact Test (HIT-6; end of baseline versus end of intervention).


Original Secondary Outcome: Same as current

Information By: University Hospital, Basel, Switzerland

Dates:
Date Received: April 11, 2017
Date Started: May 8, 2017
Date Completion: July 31, 2019
Last Updated: May 12, 2017
Last Verified: May 2017