Clinical trial NCT01831934: Responses to Influenza Vaccine in Patients With Mitochondrial Disorders (MELAS)
Official title: Metabolic and Immune Responses to TIV in Patients With Mitochondrial Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: MELAS Syndrome
Keywords: Mitochondrial disorder
Trivalent inactivated influenza vaccine
Adolescents and adults
Immune response
Metabolic response
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-04-15
Enrollment: 22
Sex: ALL
Minimum age (years): 13
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility 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.

Primary outcomes:
measure: Clinical Safety of TIV Vaccine
timeFrame: Day 0 to Day28
Secondary outcomes:
Other outcomes:
measure: Measurement of Intracellular Glutathione by Hi-D FACS (CD4 and CD8 T Cells) and Tandem Mass Spectrometry (Whole Blood)
timeFrame: Day 0-Day28
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Cornelia L Dekker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Gregory M Enns, MBChB
role: PRINCIPAL_INVESTIGATOR
References: