Ignite Creation Date:
2025-12-24 @ 6:54 PM
Ignite Modification Date:
2025-12-27 @ 7:50 AM
Study NCT ID:
NCT00605657
Status:
COMPLETED
Last Update Posted:
2013-03-21
First Post:
2008-01-15
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Valproic Acid (Depakote[Registered Trademark]) to Treat Autoimmune Lymphoproliferative Syndrome (ALPS)
Sponsor:
Koneti Rao
Organization:
Study Overview
Official Title:
Pilot (Phase I-II) Study of Valproic Acid (Depakote) for the Treatment of the Autoimmune Lymphoproliferative Syndrome (ALPS)
Status:
COMPLETED
Status Verified Date:
2013-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
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.
Detailed Description:
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.
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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 08-I-0053 | OTHER_GRANT | DIR NIAID | View |