Valproic Acid (Depakote[Registered Trademark]) to Treat Autoimmune Lymphoproliferative Syndrome (ALPS)
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|ClinicalTrials.gov Identifier: NCT00605657|
Recruitment Status : Completed
First Posted : January 31, 2008
Results First Posted : March 21, 2013
Last Update Posted : March 21, 2013
This study will test whether valproic acid (Depakote[Registered Trademark]) can shrink enlarged lymph glands and spleen in patients with autoimmune lymphoproliferative syndrome (ALPS). Depakote has been used for more than 30 years for treating various medical disorders in adults and children, including migraine headaches, seizures and psychiatric disorders. In animal studies, it was effective in shrinking both lymph nodes and spleen in animals with conditions similar to ALPS.
People with ALPS who are between 2 and 70 years of age and who have had an enlarged spleen or lymph glands for at least 1 year may be eligible for this study.
Participants take Depakote as a tablet or liquid or sprinkled on food twice a day for 16 weeks. The drug dose is increased slowly over the first 3 to 4 weeks until the maximum tolerated dose is reached. Blood tests are done at 2, 4, 6, 8 and 10 weeks after starting the drug and 1 week after the drug is stopped to check for treatment side effects. Valproic acid blood levels will be checked during drug escalation, half way through therapy, and just before the end of treatment. A physical examination and CT scan (or ultrasound of the abdomen for patients who cannot undergo CT) are done before starting treatment and at the end of the 16-week treatment period to evaluate the response to treatment.
Patients who tolerate the treatment well and show shrinkage of the lymph glands or spleen may be offered extended treatment for up to 1 year in consultation with their primary physician. During the extended treatment period, blood tests are done at home every 6 to 8 weeks to monitor for drug side effects. Follow up evaluation visits are scheduled at the NIH Clinical Center every 3 months during the extended treatment period and 3, 6, and 12 months after treatment has ended.
|Condition or disease||Intervention/treatment||Phase|
|ALPS Hypersplenism Lymphadenopathy||Drug: Valproic Acid Procedure: CT Scan Procedure: Blood Sample||Phase 1 Phase 2|
The Autoimmune Lymphoproliferative Syndrome (ALPS) is an inherited disease associated with a defect of lymphocyte apoptosis that leads to lymphoproliferation and autoimmunity. Although, there are immunosuppressive treatments for many of its complications, there currently is no safe and effective therapy for this syndrome itself.
Valproic acid has been recently used as a histone deacetylase (HDAC) inhibitor for inducing apoptosis in malignancies and is being incorporated as part of hematology/oncology clinical trials. A pilot study will be conducted on the safety and efficacy of the drug valproic acid (Depakote [R]) for the treatment of ALPS. Twelve subjects with ALPS, will be treated initially for 4 months with twice-daily administration of valproic acid at escalating doses adjusted by weight, with close monitoring of toxicity and side effects including laboratory parameters related to the drug. The effects of valproic acid treatment on lymph node and/or spleen size will be assessed by computerized tomography scan, ultrasound and physical examination. If valproic acid is effective in reducing the size of lymph nodes and/or spleen size as defined in the study design, subjects may be offered the option to continue further therapy with valproic acid for up to 1 year. The effect of treatment on other laboratory features specific to ALPS will also be assessed. Evaluating the effects of valproic acid on these clinical and laboratory parameters will help to determine if this drug demonstrates sufficient activity to warrant study in a larger randomized controlled trial.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot (Phase I-II) Study of Valproic Acid (Depakote) for the Treatment of the Autoimmune Lymphoproliferative Syndrome (ALPS)|
|Study Start Date :||January 2008|
|Actual Primary Completion Date :||September 2011|
|Actual Study Completion Date :||September 2011|
Experimental: Valproic acid
Single arm study involving oral administration of valproic acid and monitoring of its efficacy by CT scans done before and after the intervention. Blood samples were also obtained to monitor safety labs and biomarkers.
Drug: Valproic Acid
Oral administration of valproic acid
Other Name: Depakote
Procedure: CT Scan
CT scans were done before and after treating the patient with valproic acid
Other Name: Computerized Tomography
Procedure: Blood Sample
Blood samples were collected before and after the intervention to monitor blood counts and biomarkers of ALPS
- Number of Participants With Response [ Time Frame: 3 monthly (12 week) intervals ]Reduction of lymph node and/or spleen size measured by CT imaging, or physical exam and abdominal ultrasound. A clinical response is defined as a greater than 40% reduction in lymph node size and/or greater than 40% reduction in spleen size. A CT scan with contrast measured lymph node size as well as spleen size.
- To Determine Whether the Treatment Alters, in Favorable Directions, Laboratory Markers of ALPS (e.g., Number of DNT Cells, Immunoglobin Levels, Vitamin B12 Levels, IL-10 Levels, Autoantibody Titers, Fas Mediated Apoptosis) [ Time Frame: 3 monthly (12 week) intervals ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00605657
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Koneti Rao, MD||DIR, NIAID, NIH|