A Ketogenic Diet Acts on Cortical But Not Subcortical Responsivity in Migraineurs

A Ketogenic Diet Normalizes Interictal Cortical But Not Subcortical Responsivity in Migraineurs

A short ketogenic diet (KD) treatment can prevent migraine attacks and correct excessive cortical response. Here, investigators aim to prove if the KD-related changes of cortical excitability are primarily due to cerebral cortex activity or are modulated by the brainstem.

Through the stimulation of the right supraorbital division of the trigeminal nerve, there will be concurrently interictally recorded the nociceptive blink reflex (nBR) and the pain-related evoked potentials (PREP) in 18 migraineurs patients without aura before and after 1-month on KD, while in metabolic ketosis. nBR and PREP reflect distinct brain structures activation: the brainstem and the cerebral cortex respectively. It will be estimated nBR R2 component area-under-the-curve as well as PREP amplitude habituation as the slope of the linear regression between the 1st and the 2nd block of 5 averaged responses.

Study Overview

• Status: Completed
• Conditions: Migraine Disorders
• Intervention / Treatment: Dietary supplement: Ketogenic diet

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00161
    • Policlinico Umberto I

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of migraine
• Kept a headache diary for at least 1 month
• Headache onset before the age of 50

Exclusion Criteria:

• over consumption of acute pain-killers (triptan, analgesic, or ergotamine)
• pregnancy or lactation
• type I diabetes
• serious organic or psychiatric disorders that the investigators judged as having the potential to influence the trial evaluation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketogenic diet; Group of patients treated with ketogenic diet after the first neurophysiological screening.	Dietary supplement: Ketogenic diet; Diet rich in fats and poor in carbohydrate, to induce metabolic ketosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trigeminal neurophysiological changes (amplitude)	Comparison before and during ketogenic diet of trigeminal neurophysiological features in a population of patients with migraine. In particular, the nociceptive blink reflex (nBR) and the trigeminal pain-related evoked potentials (PREPs) changes of amplitude between the baseline (pre-diet) and during the diet will be used as markers of ketones activity on neural modulation. The unit of measure of the amplitude of neurophysiological evoked responses are the micronVolts (1 volt X 10^-6).	one month
Trigeminal neurophysiological changes (latencies)	Comparison before and during ketogenic diet of latencies of trigeminal neurophysiological evoked responses in a population of patients with migraine. In particular, the latency of evoked nociceptive blink reflex (nBR) and the trigeminal pain-related evoked potentials (PREPs) changes between the baseline (pre-diet) and during the diet. The unit of measure of the latency of the neurophysiological features are the milliseconds (1 sec X 10^-3).	one month
Trigeminal neurophysiological changes (slope)	Comparison before and during ketogenic diet of the habituation slope of amplitudes of repeated responses to repetitive trigeminal painful electrical stimuli in a population of patients with migraine. A repetitive stimulus induces repetitive responses from the brainstem and cerebral cortex that physiologically have a decremental trend of amplitudes, also called habituation. On the contrary, in migraineurs, there is a deficit of habituation, i.e. a lack of decremental responses, both in nociceptive blink reflex (nBR) and the trigeminal pain-related evoked potentials (PREPs). The changes induced by ketogenic diet in habituation slope will be measured. The unit of measure of the slope is the radiant degree.	one month

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza
• Investigators: Study Chair: francesco Pierelli, MD, Sapienza University of Rome

Publications and helpful links

General Publications

• Di Lorenzo C, Coppola G, Bracaglia M, Di Lenola D, Evangelista M, Sirianni G, Rossi P, Di Lorenzo G, Serrao M, Parisi V, Pierelli F. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study. J Headache Pain. 2016;17:58. doi: 10.1186/s10194-016-0650-9. Epub 2016 May 31.
• Di Lorenzo C, Coppola G, Bracaglia M, Di Lenola D, Sirianni G, Rossi P, Di Lorenzo G, Parisi V, Serrao M, Cervenka MC, Pierelli F. A ketogenic diet normalizes interictal cortical but not subcortical responsivity in migraineurs. BMC Neurol. 2019 Jun 22;19(1):136. doi: 10.1186/s12883-019-1351-1.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): June 30, 2017
• Study Completion (Actual): November 30, 2017

Study Registration Dates

• First Submitted: December 9, 2018
• First Submitted That Met QC Criteria: December 12, 2018
• First Posted (Actual): December 13, 2018

Study Record Updates

• Last Update Posted (Actual): December 13, 2018
• Last Update Submitted That Met QC Criteria: December 12, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Ketogenic Diet
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: TrigeMigKeto

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There will be no sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No