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Trial record 1 of 2 for:    "norrie disease"
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Trial of Lithium Carbonate for Treatment of Osteoporosis-pseudoglioma Syndrome

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01108068
First Posted: April 21, 2010
Last Update Posted: December 2, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Elizabeth Streeten, University of Maryland
April 20, 2010
April 21, 2010
December 2, 2015
July 2010
July 2014   (Final data collection date for primary outcome measure)
pQCT of forearm and lower leg [ Time Frame: Baseline and 6 months ]
pQCT will be done at baseline and after 6 months of lithium to assess changes in bone quality
Same as current
Complete list of historical versions of study NCT01108068 on ClinicalTrials.gov Archive Site
Fracture [ Time Frame: Baseline and 12 months ]
Fractures will be monitored from baseline to 12 months after starting lithium and will be compared to fractures occurring during the 12 months prior to starting lithium.
Same as current
Not Provided
Not Provided
 
Trial of Lithium Carbonate for Treatment of Osteoporosis-pseudoglioma Syndrome
Trial of Lithium Carbonate for Treatment of Osteoporosis Pseudoglioma Syndrome
This is a pilot study of up to 10 patients with Osteoporosis-pseudoglioma syndrome (OPPG) from the Old Order Mennonite community, who will be given lithium for 6 months and have dual energy xray absorptiometry (DXA), peripheral quantitative computerized tomography (pQCT) and lab assessment at baseline and 6 months. Studies in the mouse model of OPPG showed that lithium normalized their bone strength. Controls (n=20) will be recruited from the Old Order Mennonite community, to minimize the effects of environmental and lifestyle factors. The controls will not be given lithium. The age range of participants will be 4-64 years.

Osteoporosis-pseudoglioma (OPPG) syndrome is a very rare genetic disorder (approximately 50 cases have been reported worldwide) due to mutations in the LRP5 gene, causing blindness from birth and fragile bones (osteoporosis)in early childhood. The bony fragility can lead to recurrent fractures of major bones such as the hip (femur) and spine, leaving some children in wheelchairs.

Treatment to strengthen the bones in OPPG has primarily been with osteoporosis medications used in other fragile bone disorders of childhood and in adults, namely the bisphosphonates (eg. pamidronate, alendronate). These drugs have helped the bone strength in OPPG somewhat but have not prevented all fractures. We have observed fractures of the hip in 3 children with OPPG who we have treated, in spite of their attaining normal bone density (determined by DXA, dual xray absorptiometry) with bisphosphonates. Therefore, new treatments for OPPG are greatly needed and new methods besides DXA are needed to monitor bone strength on treatment.

A mouse model of OPPG has been created. In the mouse model of OPPG, lithium dramatically improved their bones, returning them to normal strength and preventing fractures. Lithium, which is used for people with psychiatric disease, is known to lead to higher bone strength and reduced fractures in people who are on it for psychiatric disease. Lithium has been used safely and is approved for children 12 and above. The theory is that lithium will improve bone strength in OPPG in humans, as it has in the mouse, by stimulating bone production bypassing the genetic defect in OPPG.

In this study, we plan to treat up to 10 patients with OPPG with lithium for 6 months, monitoring the response of the bones by both DXA and pQCT (peripheral quantitative computed tomography), the latter which gives information about bone quality. An IND has been obtained to use lithium in this study.

Interventional
Not Provided
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Osteoporosis Pseudoglioma
Drug: Lithium
lithium will be given for 6 months to patients with OPPG, starting at a low dose of 2.5 mg/kg daily, gradually increasing until a lithium blood level of 0.3-0.6 ng/dl is achieved.
Other Name: lithium carbonate or lithium citrate will be used
  • Experimental: Lithium
    patients with OPPG will be treated with lithium for 6 months
    Intervention: Drug: Lithium
  • No Intervention: Unaffected controls
    Family members of patients with OPPG will have DXA and pQCT to compare to OPPG patients. These unaffected participants will not receive lithium.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
5
July 2014
July 2014   (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

  • Age 4 years or greater
  • Diagnosed with osteoporosis pseudoglioma syndrome (OPPG) or a first degree relative of someone with OPPG. For diagnosis of OPPG, one of the following is required: (1) congenital blindness in a child born into a family with known OPPG where at least one affected family member has had an LRP5 mutation demonstrated or (2) a child with no known family members with OPPG who has congenital blindness, DXA Z-score < -2.0 and mutation in LRP5 documented
  • No contraindications to lithium carbonate
  • For women of child bearing age, willing to undergo urine pregnancy test

Exclusion Criteria

  • Age under 4 years
  • Not diagnosed with osteoporosis pseudoglioma (OPPG) syndrome or a first degree relative of someone with OPPG, or a member of the Old Order Mennonite community
  • Pregnant
  • For women of childbearing age, not willing to undergo urine pregnancy test
  • Contraindication to Lithium (serum creatinine > 1.3, known cardiovascular disease [history of myocardial infarction, heart failure], currently on diuretic or ACE inhibitor)
  • Glomerular filtration rate below 80 cc/min
Sexes Eligible for Study: All
4 Years to 64 Years   (Child, Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01108068
HP-40536
Yes
Not Provided
Not Provided
Elizabeth Streeten, University of Maryland
University of Maryland
Not Provided
Principal Investigator: Elizabeth A Streeten, MD University of Maryland
University of Maryland
December 2015

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