Trial of Lithium Carbonate for Treatment of Osteoporosis-pseudoglioma Syndrome

This study has been completed.
Information provided by (Responsible Party):
Elizabeth Streeten, University of Maryland Identifier:
First received: April 20, 2010
Last updated: December 1, 2015
Last verified: December 2015
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.

Condition Intervention
Osteoporosis Pseudoglioma
Drug: Lithium

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Trial of Lithium Carbonate for Treatment of Osteoporosis Pseudoglioma Syndrome

Resource links provided by NLM:

Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • pQCT of forearm and lower leg [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    pQCT will be done at baseline and after 6 months of lithium to assess changes in bone quality

Secondary Outcome Measures:
  • Fracture [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    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.

Enrollment: 5
Study Start Date: July 2010
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lithium
patients with OPPG will be treated with lithium for 6 months
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
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.

Detailed Description:

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.


Ages Eligible for Study:   4 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

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
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Please refer to this study by its identifier: NCT01108068

United States, Pennsylvania
University of Maryland Amish Research Clinic
Lancaster, Pennsylvania, United States, 17601
Sponsors and Collaborators
University of Maryland
Principal Investigator: Elizabeth A Streeten, MD University of Maryland
  More Information

Responsible Party: Elizabeth Streeten, Associate Professor of Medicine, University of Maryland Identifier: NCT01108068     History of Changes
Other Study ID Numbers: HP-40536 
Study First Received: April 20, 2010
Last Updated: December 1, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Maryland:
Osteoporosis-pseudoglioma syndrome, OPPG, LRP5 mutation

Additional relevant MeSH terms:
Genetic Diseases, X-Linked
Osteogenesis Imperfecta
Spasms, Infantile
Bone Diseases
Bone Diseases, Developmental
Bone Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Collagen Diseases
Connective Tissue Diseases
Epilepsy, Generalized
Eye Diseases
Genetic Diseases, Inborn
Musculoskeletal Diseases
Nervous System Diseases
Neurologic Manifestations
Sensation Disorders
Signs and Symptoms
Vision Disorders
Lithium Carbonate
Antidepressive Agents
Antimanic Agents
Central Nervous System Depressants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs processed this record on May 22, 2016