Role of Ketogenic Diet in SSPE

Post Measles Subacute Sclerosing Panencephalitis (SSPE)and the Role of Ketogenic Diet, A Prospective Cohort Study

SSPE is a progressive neurodegenerative disorder occurring after measles infection and is potentially life-threatening.Measles infection remains endemic in Pakistan especially in the lower socioeconomic population where the vaccine coverage is low. The ketogenic diet has been used in a large number of diseases especially intractable epilepsies in children and also in certain neurodegenerative disorders like Parkinson's and Alzheimer's in adults. Some of the case reports from India and the USA have reported the beneficial results of ketogenic diet(KD) not only in the control of myoclonic jerks of SSPE but also in stopping and reversing the progress of the disease. There is a definite need to conduct a multi-center trial of KD to establish its effectiveness in SSPE.

At the Aga khan university, the investigators have an experienced team who have been using KD for the last 9 years for intractable epilepsy. At AKU the investigators currently have 4 patients on board for the past 4 months, with diagnosed SSPE on Low Glycemic Index Diet and showing some improvement in their seizure and motor control. Based on these reports, for a poor measles control country like Pakistan, there is a need to work further in order to establish evidence for KD therapy as a treatment for SSPE. The findings of the proposed study will serve as a hope for the improvement of quality of life of patients suffering from SSPE which is a devastating disease with almost 100% mortality .

Study Overview

• Status: Not yet recruiting
• Conditions: SSPE
• Intervention / Treatment: Other: KETOGENIC DIET

Detailed Description

Methodology This will be a bi-center trial. The national institute of child health (NICH) will be a partner in this study along with Aga Khan University Hospital, Karachi. This study will be a nutritional research study looking at the role of the Ketogenic diet in improving seizures and overall disability in children with SSPE. LGIT will be the form of KD used for these patients.

All families with children who have been newly diagnosed with confirmed SSPE will be approached to start the low glycemic index diet,(liberalized kind of KD). They will be counseled on the disease and the diet regimen. all possible side effects and management will be discussed. The duration of follow-up will be for one year and there will be no potential cost incurred by the patient.

Patients will also be followed up by the physiotherapist at the physiotherapy department at AKU ( @ no cost)who will be supporting their motor rehabilitation. Investigations which include blood work and echo and ultrasound and EEGs will be done at regular intervals Sampling technique A consecutive sampling of all children who are diagnosed with SSPE will be used. A total of 26 children >2-<15 years will be enrolled over a period of two years.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shahnaz H Ibrahim, MBBS;FCPS; Phone Number: +923002119347; Email: shahnaz.ibrahim@aku.edu
• Study Contact Backup: Name: Hira Farooq, NUTRITION; Phone Number: +923152566548; Email: hira.farooq@aku.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 15 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:• All patients with a recent diagnosis of SSPE based on Dyken's criteria. Children aged ≥2 - ≤15 years.

• Having at least one member of the family residing with the patient who can read and understand directions in Urdu and /or Sindhi.

Exclusion Criteria:

• • Parents not agreeing to start the diet.

  • Age less than 2 years or over 15 years.
  • Patients who are already being given immune modulators.
  • Any other associated co-morbidity.
  • Patients having difficulty in swallowing and parents not allowing a nasogastric tube.
  • Totally uneducated family with no one who can read or write and understand directions in Urdu and/ or Sindhi.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Ketogenic Diet; This will be a prospective cohort study. All families with children who have been newly diagnosed with confirmed SSPE (based on Dyken's Criteria) will be approached to start the low glycemic index diet (liberalized kind of KD). A thorough dietary history will be taken from the parents/caregivers, and they will be counseled by a trained dietitian on the diet, all pros and cons, and the format. After the verbal agreement, formal consent will be taken from the parent/ caregiver for initiation of the diet.

Other: KETOGENIC DIET; This will be a prospective cohort study. All families with children who have been newly diagnosed with confirmed SSPE (based on Dyken's Criteria) will be approached to start the low glycemic index diet (liberalized kind of KD). A thorough dietary history will be taken from the parents/caregivers, and they will be counseled by a trained dietitian on the diet, all pros and cons, and the format. After the verbal agreement, formal consent will be taken from the parent/ caregiver for initiation of the diet. These patients are usually already admitted in the hospital for initial diagnosis and management. Therefore the initiation of the diet will be in the hospital during their admission if the parents/ caregivers agrees. A minimum of 2-3 days would be required to train the parents/caregivers.; Other Names: LOW GLYCEMIC INDEX DIET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seizure control	frequency and severity will be measured through a seizure record diary, daily number of seziures will be averaged over a month and monthly record will be evaluated as percentage increase or decrease in 3 months intervals	for a period of 6 months .

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cognitive Change ,	checked by using Pedicat with 4 domains. Daily activities, Mobility and Social/Cognitive domains.The three functional skill domains are rated on a 4 point scale: Unable; Hard; A little hard; Easy 0.I don't know Responsibility:This domain has its own 5 point scale: Adult/caregiver has full responsibility;; Adult/caregiver has most responsibility and child takes a little responsibility; Adult/caregiver and child share responsibility about equally; Child has most responsibility with a little direction, supervision or guidance from an adult/caregiver; Child takes full responsibility without any direction, supervision or guidance from an adult/caregiver Two types of score will calculate: normative scores and scaled scores. The normative score is based on the child's chronological age. Scaled score provides a way to look at current functional skills and progress in skills over times (compare the child towards itself).	base line, after 6 months of study then after and one year of study.
behavioral Change	this will be checked by using modified Ashworth scales.MODIFIED ASHWORTH The modified Ashworth scale is a muscle tone assessment scale used to assess the resistance experienced during passive range of motion, which does not require any instrumentation and is quick to perform. scoring 0 No increase in tone 1 slight increase in tone giving a catch when slight increase in muscle tone, manifested by the limb was moved in flexion or extension. 1+ slight increase in muscle tone, manifested by a catch followed by minimal resistance throughout (ROM ) 2 more marked increase in tone but more marked increased in muscle tone through most limb easily flexed 3 considerable increase in tone, passive movement difficult 4 limb rigid in flexion or extension	base line, after 6 months of study then after and one year of study
motor developmental Change	this will be checked by , Modified Rankin and GMFM Modified Rankin Scale Score Description 0 No symptoms at all; No significant disability despite symptoms; Slight disability; Moderate disability; Moderately severe disability; Severe disability; Dead GMFM There is a scoring system with each item scored as 0, 1, 2, 3, or "not tested". A scoring key of 0 - does not initiate, 1 - initiates, 2 - partially completes, and 3 - completed, is used; however parameters such as distance, time, support provided, accuracy, counts, and tasks will determine specific item scores. Items that a child refuses to attempt despite reason they may be able to perform at least partially or items not administered are scored as 'not tested'. The scoring system of the GMFM is a four-point scale that consists of 66 items divided into five dimensions of gross motor function:(a) lying and rolling, (b) sitting, (c) crawling and kneeling, (d) standing, and (e) walking, running and jumping.	base line, after 6 months of study then after and one year of study

Collaborators and Investigators

• Sponsor: Aga Khan University
• Collaborators: National Institute of Child Health, Karachi, Pakistan
• Investigators: Principal Investigator: Shahnaz H Ibrahim, MBBS ;FCPS, AKU

Publications and helpful links

General Publications

• Ibrahim SH, Amjad N, Saleem AF, Chand P, Rafique A, Humayun KN. The upsurge of SSPE--a reflection of national measles immunization status in Pakistan. J Trop Pediatr. 2014 Dec;60(6):449-53. doi: 10.1093/tropej/fmu050. Epub 2014 Sep 16.
• Rafique A, Amjad N, Chand P, Zaidi SS, Rana MS, Ahmed K, Ibrahim S. Subacute sclerosing panencephalitis: clinical and demographic characteristics. J Coll Physicians Surg Pak. 2014 Aug;24(8):557-60.

Helpful Links

• Jafri SK, Kumar R, Ibrahim SH. Subacute sclerosing panencephalitis - current perspectives. Pediatric Health Med Ther. 2018;9:67-71

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): December 10, 2021

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 22, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Ketogenic Diet; Progressive Neurological Disorder; Intractable Epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Slow Virus Diseases; Encephalitis; Measles; Neuroinflammatory Diseases; Subacute Sclerosing Panencephalitis
• Other Study ID Numbers: 2021-6491-19410.

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No