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

• ClinicalTrials.gov Identifier: NCT01831934
• Recruitment Status: Completed
• First Posted: April 15, 2013
• Results First Posted: April 21, 2017
• Last Update Posted: May 30, 2017
• Sponsor: Stanford University
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Cornelia L. Dekker, Stanford University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
MELAS Syndrome	Biological: Fluzone®	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Metabolic and Immune Responses to TIV in Patients With Mitochondrial Disease
• Study Start Date: September 2010
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: March 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Clinical Safety of TIV Vaccine [ Time Frame: Day 0 to Day28 ]
   We will measure solicited local and systemic adverse events and SAEs for 1 month following immunization

Other Outcome Measures:

1. Measurement of Intracellular Glutathione by Hi-D FACS (CD4 and CD8 T Cells) and Tandem Mass Spectrometry (Whole Blood) [ Time Frame: Day 0-Day28 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 13 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Cornelia L Dekker, MD; Stanford University
• Principal Investigator: Gregory M Enns, MBChB; Stanford University

More Information

Additional Information:

Stanford-LPCH Vaccine Program website for clinical trials 

• Responsible Party: Cornelia L. Dekker, Professor, Pediatrics, Stanford University
• ClinicalTrials.gov Identifier: NCT01831934
• Other Study ID Numbers: SU-18615; R21HD061709-01A1 ( U.S. NIH Grant/Contract )
• First Posted: April 15, 2013
• Results First Posted: April 21, 2017
• Last Update Posted: May 30, 2017
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cornelia L. Dekker, Stanford University:

Mitochondrial disorder; Trivalent inactivated influenza vaccine; Adolescents and adults; Immune response; Metabolic response

Additional relevant MeSH terms:

MELAS Syndrome; Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Muscular Diseases; Musculoskeletal Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Neuromuscular Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Mitochondrial Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs