Responses to Influenza Vaccine in Patients With Mitochondrial Disorders (MELAS)

Metabolic and Immune Responses to TIV in Patients With Mitochondrial Disease

This pilot clinical study evaluated the safety and metabolic responses to a licensed inactivated seasonal influenza vaccine (TIV) in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) volunteers and controls.

Study Overview

• Status: Completed
• Conditions: MELAS Syndrome
• Intervention / Treatment: Biological: Fluzone®

Detailed Description

This pilot clinical study evaluated the safety and metabolic responses to a licensed inactivated seasonal influenza vaccine (TIV). This study will consist of two cohorts: MELAS syndrome volunteers (a specific identified disorder of mitochondrial dysfunction: mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) between 13-60 years OR adult control volunteers between 18-65 years of age. Both cohorts will receive the same treatment: a single vaccination with an FDA-licensed intramuscular seasonal trivalent inactivated influenza vaccine (TIV).

All participants will receive a single administration of a licensed influenza vaccine. Prior to vaccination, participants will provide information regarding health history and responses to health questionnaires. A blood sample and urine specimen were collected prior to vaccination, and at 6 hours, 5-7 days and 26-30 days post-immunization.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:Inclusion criteria include:

• Age between 13-60 years for MELAS volunteers OR age between 18-65 years for adult control volunteers. Control volunteers will be age-matched +/-5 years to enrolled MELAS volunteers. If the MELAS volunteer has diabetes and uses insulin daily, their control will be an adult with diabetes who uses insulin daily.
• General good health at time of enrollment
• Willing and able to sign Informed Consent
• Available for follow-up for the planned duration of the study
• Acceptable medical history by screening evaluation and brief clinical assessment
• All female participants of childbearing potential must use an acceptable method of contraception and not become pregnant for the duration of the clinical phase of the study (approximately 1 month to completion of Visit 4). (Acceptable contraception may include but is not limited to implants, injectables, combined oral contraceptives, effective intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner).

Exclusion Criteria:Exclusion criteria will include:

• Allergy to egg or egg products or allergy to vaccine components, including thimerosal
• Active systemic or serious concurrent illness, including febrile illness, within the 3 days prior to study vaccination
• History of immunodeficiency, known or suspected impairment of immunologic function, including, but not limited to, clinically significant liver disease, moderate to severe renal disease, or any other chronic disorder which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.
• Blood pressure >150 systolic or >95 diastolic at Visit 1.
• Hospitalization in the past year for congestive heart failure or emphysema.
• History of chronic Hepatitis B or C.
• Recent or current use of immunosuppressive medication, including glucocorticoids (corticosteroid nasal sprays are permissible).
• Malignancy, other than squamous cell or basal cell skin cancer (includes solid tumors such as breast cancer or prostate cancer with recurrence in the past year, and any hematologic cancer such as leukemia).
• Autoimmune disease (including rheumatoid arthritis treated with immunosuppressive medication such as Plaquenil, methotrexate, prednisone, Enbrel) which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.
• History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
• Receipt of blood or blood products within the past 6 months
• Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol
• Inactivated vaccine 14 days prior to vaccination or live, attenuated vaccine within 60 days of vaccination
• History of Guillain-Barré Syndrome
• Pregnant or lactating woman
• Use of investigational agents within 30 days prior to enrollment
• Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment
• Any condition which, in the opinion of the investigator, might interfere with volunteer safety, study objectives or the ability of the participant to understand or comply with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MELAS group:13-60 years of age.; Fluzone® 2010-2011 Formula or 2011-2012 depending on year	Biological: Fluzone®; This vaccine is given intramuscularly, either the 2010-2011 or 2011-2012 vaccination was given as appropriate; Other Names: trivalent inactivated influenza vaccine (TIV); FDA-licensed seasonal influenza vaccine
Experimental: Control Group: 18-65 years of age; Fluzone® 2010-2011 Formula or 2011-2012 depending on year	Biological: Fluzone®; This vaccine is given intramuscularly, either the 2010-2011 or 2011-2012 vaccination was given as appropriate; Other Names: trivalent inactivated influenza vaccine (TIV); FDA-licensed seasonal influenza vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Safety of TIV Vaccine	We will measure solicited local and systemic adverse events and SAEs for 1 month following immunization	Day 0 to Day28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Intracellular Glutathione by Hi-D FACS (CD4 and CD8 T Cells) and Tandem Mass Spectrometry (Whole Blood)	This method relies on the ability of intracellular glutathione S-transferases to tag GSH to bimane to yield a bimane-GS conjugate that fluoresces at 440 nm.	Day 0-Day28

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Gregory M Enns, MBChB, Stanford University

Publications and helpful links

Helpful Links

• Stanford-LPCH Vaccine Program website for clinical trials

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: March 19, 2013
• First Submitted That Met QC Criteria: April 10, 2013
• First Posted (Estimate): April 15, 2013

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Immune response; Metabolic response; Mitochondrial disorder; Trivalent inactivated influenza vaccine; Adolescents and adults
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Mitochondrial Diseases; Brain Diseases, Metabolic, Inborn; Cerebral Small Vessel Diseases; Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; MELAS Syndrome; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: SU-18615; R21HD061709-01A1 (U.S. NIH Grant/Contract)

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