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Completed

NCT Number: NCT00825591

Biological Clock Dysfunction in Optic Nerve Hypoplasia

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.

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Key information

Conditions

Biological Clock Dysfunction Agenesis of Corpus Callosum Congenital Abnormalities Congenital Cranial Dysinnervation Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cranial Nerve Diseases Eye Diseases Eye Diseases, Hereditary Genetic Diseases, Inborn Nervous System Diseases Nervous System Malformations Ocular Motility Disorders Oculomotor Nerve Diseases Optic Nerve Diseases Optic Nerve Hypoplasia Septo-Optic Dysplasia

Age range

2 year–10 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

About this study

Objectives and Hypotheses. Our objectives are to define the scope and problems related to biological clock disorders in children with ONH and to develop effective treatments for this condition. Based on our observations, we hypothesize: (1) Daily rest-activity patterns and sleep will be abnormal in up to 50% of children with ONH. (2) It is possible to identify risk factors for abnormal circadian system function and sleep problems in ONH. (3) Nocturnal melatonin administration will improve abnormal sleep and activity patterns in children with ONH.

Design: These studies will involve collaborative efforts between Yale University and Dr. Mark Borchert of Childrens Hospital Los Angeles, who follows the largest population of children with ONH in the world. We will study children ages 2-10 years with documented ONH using standard criteria. Based on these criteria, we have more than 100 eligible patients.

To test our hypotheses, we will: (1) examine expressed rhythmicity in children with ONH. These studies will use actigraphy, sleep questionnaires, and assessment of melatonin secretory profiles. (2) We will correlate hypothalamic anatomical abnormalities and the degree endocrine dysfunction with sleep and expressed rhythmicity. (3) We will test if short-term administration of melatonin improves sleep-wake patterns in children with abnormally-expressed rhythmicity.

Potential Impact: Our preliminary data raise the possibility that children with ONH will have circadian system dysfunction resulting in abnormal rhythmicity and sleep. However, to date there have been no formal attempts to identify children with ONH who are at risk for such problems, nor have there been efforts aimed at developing potential treatments. The proposed prospective clinical study will represent an important attempt to identify a group of children with circadian system dysfunction.

At the completion of this study, we anticipate having determined risk factors for circadian system dysfunction in children with ONH. Insights gained from these studies should lead to the development of new approaches for treating circadian clock lesions in ONH, with the hope of improving the well-being of circadian system function in the boys and girls with this condition.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

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

Treatment and study plan

melatonin

Dietary Supplement

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

Placebo Comparator

Dietary Supplement

Oral administration before bed. 6 week duration.

Primary outcomes

  1. Assessment of rest-activity patterns

    Time frame: two years

Sponsors and collaborators

Lead sponsor

Yale University

Other

Collaborators

  • Children's Hospital Los Angeles

Registry information

Official study title

Identification and Treatment of Biological Clock Dysfunction in Optic Nerve Hypoplasia

Important dates

Study start
2008
Primary completion
2011
Study completion
2011
First posted
Jan 21, 2009
Registry last updated
Sep 25, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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