Trial record 2 of 2 for:    Septo-Optic Dysplasia

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
  Purpose

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.


Condition Intervention Phase
Biological Clock Dysfunction
Optic Nerve Hypoplasia
Dietary Supplement: Melatonin
Dietary Supplement: Placebo Comparator
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Diagnostic
Official Title: Identification and Treatment of Biological Clock Dysfunction in Optic Nerve Hypoplasia

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Assessment of rest-activity patterns [ Time Frame: two years ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: October 2008
Estimated Study Completion Date: September 2011
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Individuals with abnormal rhythmicity will be treated with melatonin to assess if sleep patterns are improved.
Dietary Supplement: Melatonin
Oral administration before bed. We will test two doses (0.5 or 3.0 mg/m2. 6 week duration.)
Placebo Comparator: 2 Dietary Supplement: Placebo Comparator
Oral administration before bed. 6 week duration.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   2 Years to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00825591

Locations
United States, California
Children's Hospital of Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Joyce Sutedja    323-361-6219    jsutedja@chla.usc.edu   
Sponsors and Collaborators
Yale University
Children's Hospital Los Angeles
Investigators
Study Director: Casandra Fink Children's Hospital Los Angeles
  More Information

No publications provided

Responsible Party: Esther Nakamura-Reyes, Childrens Hospital of Los Angeles
ClinicalTrials.gov Identifier: NCT00825591     History of Changes
Other Study ID Numbers: 0804003699, TRSH-SAR
Study First Received: October 13, 2008
Last Updated: February 7, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
optic nerve hypoplasia
septo-optic dysplasia
melatonin
circadian rhythm

Additional relevant MeSH terms:
Melatonin
Antioxidants
Central Nervous System Agents
Central Nervous System Depressants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014