Biological Clock Dysfunction in Optic Nerve Hypoplasia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by Yale University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Children's Hospital Los Angeles
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
NCT00825591
First received: October 13, 2008
Last updated: February 7, 2011
Last verified: February 2011

October 13, 2008
February 7, 2011
October 2008
September 2011   (final data collection date for primary outcome measure)
Assessment of rest-activity patterns [ Time Frame: two years ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00825591 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
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Biological Clock Dysfunction in Optic Nerve Hypoplasia
Identification and Treatment of 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.

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.

Interventional
Phase 0
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Diagnostic
  • Biological Clock Dysfunction
  • Optic Nerve Hypoplasia
  • Dietary Supplement: Melatonin
    Oral administration before bed. We will test two doses (0.5 or 3.0 mg/m2. 6 week duration.)
  • Dietary Supplement: Placebo Comparator
    Oral administration before bed. 6 week duration.
  • Active Comparator: 1
    Individuals with abnormal rhythmicity will be treated with melatonin to assess if sleep patterns are improved.
    Intervention: Dietary Supplement: Melatonin
  • Placebo Comparator: 2
    Intervention: Dietary Supplement: Placebo Comparator
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
September 2011
September 2011   (final data collection date for primary outcome measure)

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
Both
2 Years to 10 Years
No
United States
 
NCT00825591
0804003699, TRSH-SAR
No
Esther Nakamura-Reyes, Childrens Hospital of Los Angeles
Yale University
Children's Hospital Los Angeles
Study Director: Casandra Fink Children's Hospital Los Angeles
Yale University
February 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP