- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00825591
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.
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90027
- Children's Hospital of Los Angeles
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: 2
|
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.
|
Oral administration before bed.
We will test two doses (0.5 or 3.0 mg/m2.
6 week duration.)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Assessment of rest-activity patterns
Time Frame: two years
|
two years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Casandra Fink, Children's Hospital Los Angeles
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Eye Diseases
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Eye Diseases, Hereditary
- Optic Nerve Diseases
- Cranial Nerve Diseases
- Nervous System Malformations
- Optic Nerve Hypoplasia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Protective Agents
- Antioxidants
- Melatonin
Other Study ID Numbers
- 0804003699
- TRSH-SAR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Biological Clock Dysfunction
-
Sakarya UniversityCompletedSleep Quality | Circadian Rhythm | Chronobiology Disorders | Nursing Care | Biological Clock DisturbanceTurkey
-
Shengjing HospitalUnknownGeneral Anesthesia | Elderly Patients | Postoperative Cognitive Function | Circadian ClockChina
-
Fundació EurecatCirce, S.L.Not yet recruiting
-
Centre Hospitalier Universitaire, AmiensRecruitingBiological SamplesFrance
-
DaacroISTITUTO KURZ ITALIA S.R.L.; Institut Kurz GmbH; Fattoria La Vialla di Gianni...CompletedBiological AvailabilityGermany
-
Wageningen UniversityCompletedBiological Availability
-
Alza Corporation, DE, USACompleted
-
Janssen Infectious Diseases BVBACompletedHealthy | Biological AvailabilityNetherlands
-
University of Massachusetts, AmherstNational Institutes of Health (NIH); National Institute on Aging (NIA); University...Recruiting
-
PfizerCompletedBiological AvailabilityUnited States
Clinical Trials on Melatonin
-
Duquesne UniversityCompleted
-
Peking Union Medical College HospitalCompleted
-
UnivatesAline Patrícia Brietzke; Ana Paula CostellaRecruitingPerimenopausal DisorderBrazil
-
Qazvin University Of Medical SciencesCompletedPost Partum Haemorrhage in Patients Undergoing Cesarean SectionIran, Islamic Republic of
-
Chinese PLA General HospitalUnknown
-
Assaf-Harofeh Medical CenterNeurim Pharmaceuticals Ltd.UnknownMild Cognitive Impairment (MCI)Israel
-
Pharmavite LLCKGK Science Inc.Completed
-
Ain Shams UniversityCompletedCerebral Palsy | Growth | Children, Only | MelatoninEgypt
-
Mayo ClinicRecruitingParkinson Disease | Rapid Eye Movement Sleep Behavior DisorderUnited States
-
Providence Health & ServicesCompletedRelapsing Remitting Multiple SclerosisUnited States