Histidine Therapy: A Project to Treat HARS Deficiency

Lawson Health Research Institute

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: HARS Syndrome

Treatments: Dietary Supplement: L-Histidine

Study type: Interventional

Funder types: Other

Identifiers

NCT02924935

108364

Details and patient eligibility

About

This study evaluates the role of histidine in patients with HARS Syndrome. Children with HARS Syndrome will receive oral nutritional supplementation with histidine at a dose which will be increased in the event of acute febrile illness. Vision, hearing and plasma biomarkers will be monitored throughout the study period.

Full description

HARS syndrome is a progressive degenerative disease affecting eyesight and hearing caused by a mutation in the HARS gene which codes for an enzyme involved in protein synthesis. HARS syndrome has been exclusively found in the Old Order Amish communities in Southwestern Ontario and in Pennsylvania. Children with this disorder initially have normal vision and hearing, but with a febrile illness, can have a sudden loss of vision and hearing, as well as visual hallucinations. There is some evidence that vision loss progresses, albeit at a slower rate, even without a febrile incident. In more severe cases, fluid accumulates in the lungs (acute respiratory distress syndrome or ARDS) which can cause a drop in oxygen levels and sometimes death. There is currently no specific treatment for HARS syndrome, apart from supportive care. Anecdotal evidence of an adult with HARS syndrome who was treated with the amino acid L-histidine suggests that there was an improvement in vision, however there were no baseline objective measurements of vision prior to the use of histidine. We have designed a pilot project in which histidine will be given to children with HARS for 6 months. Investigators hypothesize that the histidine will be well tolerated and easily administered, without side effects. Investigators will monitor vision, hearing and bloodwork to determine if there is any change during the course of treatment. As well, investigators plan to administer increased doses of histidine during acute illnesses, hoping to prevent deterioration in breathing due to ARDS. The results of this initial pilot project may pave the way for a longer term study of the use of histidine.

Enrollment: 14 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Have molecularly confirmed HARS syndrome (Y454S homozygous).
2. Capable of giving informed consent or assent, or have an acceptable surrogate capable of giving consent on the participant's behalf.
3. Participant or surrogate decision maker is able to understand the study procedures and comply with them throughout the course of the study.
4. Able to take solid foods (ie applesauce) or swallow capsules (in younger children, capsule may be broken and contents mixed with applesauce).
5. At least 1 year of age or greater than 8 kg in weight (since histidine is supplied as a minimal dose of 500 mg/capsule.

Exclusion criteria

1. Unable or unwilling to give informed consent.
2. Unable to understand instructions or unable to attend clinic visits.
3. Children less than 1 year of age or less than ~8kg in weight (since histidine is supplied as 500 mg capsules).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 1 patient group

Treatment

Experimental group

Description:

L-Histidine in 500mg capsules taken at a dose of 50mg/kg to maintain high-normal serum histidine levels

Treatment:

Dietary Supplement: L-Histidine