Biological Clock Dysfunction in Optic Nerve Hypoplasia

NCT00825591 | Completed Early Phase 1

• 2 other identifiers: 0804003699TRSH-SAR
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Optic Nerve Hypoplasia (ONH) is a leading cause of blindness in children. For unclear reasons, the incidence of ONH is increasing, with ONH affecting about 1 in 10,000 live-born infants. In addition to visual deficits, ONH is associated with varying degrees of hypopituitarism, developmental delay, brain malformations and obesity. Although genetic mutations have been rarely observed to result in ONH, the causes of ONH are largely not known. In limited anatomical observations, the suprachiasmatic nuclei (SCN) located in the anterior hypothalamus, which generate circadian rhythms, have been observed to be abnormal in children with ONH. Thus, children with ONH may have biological clock dysfunction. In collaborative studies with Dr. Mark Borchert of Childrens Hospital Los Angeles (CHLA), we have recently discovered that one-half of children with ONH have grossly abnormal sleep-wake patterns, as assessed by actigraphy. Although not known for children with ONH, abnormal sleep-wake patterns have been observed to be associated with neurocognitive impairment and obesity. We also observe that nocturnal melatonin administration can improve abnormal sleep-wake cycles in these children, raising the possibility that it will be possible to treat abnormal rhythmicity in children with ONH.

Conditions

Biological Clock Dysfunction; Optic Nerve Hypoplasia

Keywords

optic nerve hypoplasia; septo-optic dysplasia; melatonin; circadian rhythm

Outcome Measures

Primary Outcomes (1)

• Assessment of rest-activity patterns

  two years

Study Arms (2)

1

ACTIVE COMPARATOR

Individuals with abnormal rhythmicity will be treated with melatonin to assess if sleep patterns are improved.

Dietary Supplement: Melatonin

2

PLACEBO COMPARATOR

Dietary Supplement: Placebo Comparator

Interventions

Melatonin DIETARY_SUPPLEMENT

Oral administration before bed. We will test two doses (0.5 or 3.0 mg/m2. 6 week duration.)

1

Placebo Comparator DIETARY_SUPPLEMENT

Oral administration before bed. 6 week duration.

2

Eligibility Criteria

• Age: 2 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Confirmed diagnosis of ONH (Diagnosis will be confirmed by ocular fundus photography.Disc-macula distance 0.35 or below. In eyes without ONH, the DD/DM ratio is greater than 0.3581.)
• Ages 2-10 years
• Ability to ambulate independently
• Under care of endocrinologist if on pituitary hormone replacement therapy.

You may not qualify if:

• Non-ambulatory
• Active malignancy
• Cardio-respiratory disorder

Sponsors & Collaborators

• Yale University: lead
• Children's Hospital Los Angeles: collaborator

Study Sites (1)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

MeSH Terms

Conditions

Optic Nerve Hypoplasia; Septo-Optic Dysplasia

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Nervous System Malformations; Eye Diseases, Hereditary; Eye Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Congenital Cranial Dysinnervation Disorders; Oculomotor Nerve Diseases; Ocular Motility Disorders; Agenesis of Corpus Callosum

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Casandra Fink

  Children's Hospital Los Angeles

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 13, 2008
• First Posted: January 21, 2009
• Study Start: October 1, 2008
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: September 25, 2020

Record last verified: 2020-09

Locations

US (1)