Understanding the Mechanism(s) of Action on the Modified Atkins Diet for Epilepsy: Human Brain Tissues

NCT02565966 | Completed

• 1 other identifier: 14-01069
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to better define the potential molecular and anti-inflammatory changes induced by the modified Atkins diet in the brains of patients with treatment resistant epilepsy. The investigators plan to enroll 30 subjects overall in this study to compare serologic and brain tissue specimens. At NYU, investigators plan to enroll 20 subjects; an estimated ten (10) subjects will consume a modified Atkins diet for 3-4 weeks prior to surgery and an estimated ten (10) subjects will consume a non-modified, higher carbohydrate diet. Investigators at Saint Barnabas Medical Center plan to enroll 10 subjects in this study to compare serologic and brain tissue specimens. Approximately five (5) subjects will consume a modified Atkins diet for 3-4 weeks prior to surgery and five (5) subjects will consume a non-modified, higher carbohydrate diet. Blood and brain tissue specimens will be obtained at the time of surgery and will be compared. The goal of this study is to identify whether or not there are changes in neuroinflammation or neuroexcitability in the human brain induced by the modified Atkins diet.

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (8)

• Neuroinflammation markers in blood

  As measured by level of cytokines IL-6, TNF alpha, and C-reactive protein in blood samples

  At time of surgery (approximately 3-4 weeks after randomization)

• Metabolism

  As measured by level of fasting lipid profile, acylcarnitine profile, and beta-hydroxybutyrate in blood

  At time of surgery (approximately 3-4 weeks after randomization)

• Neuroinflammation markers in brain tissue

  As measured by level of cytokines, IL6, TNF alpha, and microglial activation and proliferation in brain tissue obtained during durgery

  At time of surgery (approximately 3-4 weeks after randomization)

• Levels of leptin in brain tissue

  At time of surgery (approximately 3-4 weeks after randomization)

• Levels of adenosine in brain tissue

  At time of surgery (approximately 3-4 weeks after randomization)

• Levels of adenosine kinase in brain tissue

  At time of surgery (approximately 3-4 weeks after randomization)

• Levels of adenosite-1 (A1) receptors in brain tissue

  At time of surgery (approximately 3-4 weeks after randomization)

• Levels of enzymes that synthesize glutamate and GABA

  As measured in brain tissue obtained during surgery

  At time of surgery (approximately 3-4 weeks after randomization)

Study Arms (2)

Modified Atkins Diet (MAD)

EXPERIMENTAL

Other: Modified Atkins Diet (MAD)

Normal Diet

NO INTERVENTION

Those patients in the normal diet (no intervention) group will also meet with the epilepsy center nutritionist to review the food diary and completion of this document, similar to those in the intervention (MAD) group. No dietary restrictions will be made in this group.

Interventions

Modified Atkins Diet (MAD) OTHER

For those in the MAD intervention group, the dietitian trains the patient and family in the preparation and management of this specialized therapy including sick-day guidelines, meal planning, carbohydrate counting and trouble-shooting. Written and verbal education including, but not limited to: recipes, education materials, sample meal plans and carbohydrate counters are provided to the patient during the initial education session. The caregiver/patient is trained in the outpatient setting and the diet is implemented at home with as much email/phone support from the dietician and ketogenic team as the patient needs to successfully maintain the diet. Medications are all changed over to the lowest carbohydrate forms to eliminate excess carbohydrate intake and all patients are started on vitamin supplements to maintain adequate nutrition.

Modified Atkins Diet (MAD)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients scheduled for epilepsy surgery at New York Langone Medical Center or St Barnabas Medical Center will be eligible for enrollment.
• Patient is at least 18 years of age
• Patient is willing to participate by complying with the modified Atkins diet 3 - 4 weeks prior to surgery and maintain a thorough food diary (Intervention study group) or to continue their usual diet and maintain a thorough food diary (Nonintervention study group)
• Patient/ his/her parent, caregiver, or health care proxy is willing and able to provide consent or assent

You may not qualify if:

• Patients under the age of 18 will be excluded
• Patients in whom a two-stage surgery is planned without any resection of brain tissue during the initial craniotomy
• Patients unwilling to comply with modified Atkins diet 3 -4 weeks prior to surgery or unwilling to maintain a thorough food diary will be excluded.

Sponsors & Collaborators

• NYU Langone Health: lead
• St. Barnabas Medical Center: collaborator

Study Sites (2)

Institute of Neurology and Neurosurgery at Saint Barnabas

Livingston, New Jersey, 07039, United States

Location

NYU Langone Epilepsy Center

New York, New York, 10016, United States

Location

Related Publications (1)

• Leitner DF, Siu Y, Korman A, Lin Z, Kanshin E, Friedman D, Devore S, Ueberheide B, Tsirigos A, Jones DR, Wisniewski T, Devinsky O. Metabolomic, proteomic, and transcriptomic changes in adults with epilepsy on modified Atkins diet. Epilepsia. 2023 Apr;64(4):1046-1060. doi: 10.1111/epi.17540. Epub 2023 Feb 24.

  PMID: 36775798 DERIVED

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Orrin Devinsky, MD

  NYU Langone Epilepsy Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2015
• First Posted: October 1, 2015
• Study Start: June 1, 2014
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

US (2)