Clinical trial NCT00000790: Thalidomide for Treatment of Oral and Esophageal Aphthous Ulcers and HIV Viremia in Patients With HIV Infection
Official title: Thalidomide for Treatment of Oral and Esophageal Aphthous Ulcers and HIV Viremia in Patients With HIV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Stomatitis, Aphthous
Keywords: Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Thalidomide
Stomatitis, Aphthous
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Andrulis Pharmaceuticals
First posted: 2001-08-31
Enrollment: 164
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: PRIMARY: To evaluate the effectiveness and safety of thalidomide for treatment of oral and esophageal aphthous ulcers (those unrelated to a known infection or malignancy) in patients with advanced HIV disease. To evaluate the effect of thalidomide on HIV load in this patient population. Per 06/28/94 amendment, to evaluate the effectiveness of thalidomide in preventing recurrences in patients whose aphthae completely heal at the end of acute treatment.

SECONDARY: To evaluate the effect of thalidomide on blood tumor necrosis factor (TNF) levels and to obtain pharmacokinetic data on the drug. Per 06/28/94 amendment, to evaluate the safety of thalidomide. Per 05/10/95 amendment, to explore in a substudy the effects of thalidomide on idiopathic genital aphthous ulcers in HIV-infected women.

Aphthous ulcers of the mouth or esophagus can interfere with eating, resulting in malnutrition and wasting. Thalidomide has been proposed as an effective therapy for severe forms of aphthous ulceration in AIDS patients.

Detailed description: Aphthous ulcers of the mouth or esophagus can interfere with eating, resulting in malnutrition and wasting. Thalidomide has been proposed as an effective therapy for severe forms of aphthous ulceration in AIDS patients.

Patients are randomized to receive 4 weeks of either thalidomide or placebo orally, administered once daily. Patients are followed weekly. Complete responders after 4 weeks of acute treatment enter a 24-week maintenance phase. A pharmacokinetic substudy will be included.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Anti-HIV therapy provided therapy has remained constant in the 4 weeks prior to study entry.
* Narcotic analgesia after the first week of treatment ONLY IF the patient is not experiencing somnolence.

Patients must have:

* Documented HIV infection or AIDS.
* Biopsy-confirmed aphthous ulceration of the mouth or esophagus lasting at least 2 weeks.
* Negative culture of ulcer for Herpes simplex.
* En face diameter of \>= 5 mm for largest aphthous ulcer.
* Life expectancy of at least 3 months.

NOTE:

* This study is approved for prisoner participation.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Known allergy to thalidomide.
* Grade 2 or worse bilateral peripheral neuropathy.

EXCLUDED FOR MAINTENANCE PHASE:

* Toxicity other than somnolence in acute phase that required discontinuation of drug.

Concurrent Medication:

Excluded:

* Acute therapy for opportunistic infection.
* ddC.
* Pentoxifylline.
* Methotrexate, trimetrexate, antineoplastic alkylating agents.
* Other putative immunomodulators.
* CNS depressants and/or medications with sedative or hypnotic effect.
* Systemic and/or oral topical corticosteroids.
* Systemic chemotherapy for Kaposi's sarcoma or other malignancies.
* Compounded antibacterial mouthwashes containing anti-infective agents (such as doxycycline, minocycline, tetracycline, or nystatin).

Concurrent Treatment:

Excluded:

* Radiation to head and/or neck.

Patients with the following prior conditions are excluded:

* History of grade 2 or worse bilateral peripheral neuropathy.
* Change in anti-HIV therapy within 4 weeks prior to study entry.
* Prior enrollment in ACTG 251 or prior treatment of aphthous ulcers with thalidomide.

Prior Medication:

Excluded:

* Systemic and/or oral topical corticosteroids within 1 week prior to first set of bloods drawn.
* Other putative immunomodulators within 2 weeks prior to study entry.
* Prior thalidomide for aphthous ulcers.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Univ of Southern California / LA County USC Med Ctr
state: California
city: San Francisco
country: United States
facility: San Francisco AIDS Clinic / San Francisco Gen Hosp
state: California
city: San Francisco
country: United States
facility: Stanford at Kaiser / Kaiser Permanente Med Ctr
state: California
city: Torrance
country: United States
facility: Harbor UCLA Med Ctr
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Washington
country: United States
facility: Howard Univ
state: District of Columbia
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Honolulu
country: United States
facility: Queens Med Ctr
state: Hawaii
city: Honolulu
country: United States
facility: Univ of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Chicago
country: United States
facility: Louis A Weiss Memorial Hosp
state: Illinois
city: Chicago
country: United States
facility: Illinois Masonic Med Ctr
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Boston
country: United States
facility: Harvard (Massachusetts Gen Hosp)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess - West Campus
state: Massachusetts
city: Bronx
country: United States
facility: Bronx Municipal Hosp Ctr/Jacobi Med Ctr
state: New York
city: Bronx
country: United States
facility: Comprehensive Health Care Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Montefiore Adolescent AIDS Prog / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Montefiore Family Health Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Jack Weiler Hosp / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Montefiore Med Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: North Central Bronx Hosp / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Bronx Veterans Administration / Mount Sinai Hosp
state: New York
city: Buffalo
country: United States
facility: SUNY / Erie County Med Ctr at Buffalo
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr / Pediatrics
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: Syracuse
country: United States
facility: SUNY / State Univ of New York
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve Univ
state: Ohio
city: Hershey
country: United States
facility: Milton S Hershey Med Ctr
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson Univ Hosp
state: Pennsylvania
city: Nashville
country: United States
facility: Meharry Med College
state: Tennessee
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico
Study officials:
name: Jacobson JM
role: STUDY_CHAIR
References:
citation: Jacobson JM, Spritzler J, Fox L, Fahey JL, Jackson JB, Chernoff M, Wohl DA, Wu AW, Hooton TM, Sha BE, Shikuma CM, MacPhail LA, Simpson DM, Trapnell CB, Basgoz N. Thalidomide for the treatment of esophageal aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group. J Infect Dis. 1999 Jul;180(1):61-7. doi: 10.1086/314834.
citation: Jacobson JM, Greenspan JS, Spritzler J, Ketter N, Fahey JL, Jackson JB, Fox L, Chernoff M, Wu AW, MacPhail LA, Vasquez GJ, Wohl DA. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. 1997 May 22;336(21):1487-93. doi: 10.1056/NEJM199705223362103.
citation: Gilden D. Thalidomide and aphthous ulcers. GMHC Treat Issues. 1995 Nov;9(11):12.
citation: Jacobson JM, Greenspan JS, Spritzler J, Fox L, Fahey JL, Jackson JB, Chernoff M, Wohl DA, Pulvirenti JJ, Hooton TM, Shikuma C. Thalidomide in low intermittent doses does not prevent recurrence of human immunodeficiency virus-associated aphthous ulcers. J Infect Dis. 2001 Jan 15;183(2):343-346. doi: 10.1086/317928. Epub 2000 Dec 15.
citation: Aweeka F, Trapnell C, Chernoff M, Jayewardene A, Spritzler J, Bellibas SE, Lizak P, Jacobson J. Pharmacokinetics and pharmacodynamics of thalidomide in HIV patients treated for oral aphthous ulcers: ACTG protocol 251. AIDS Clinical Trials Group. J Clin Pharmacol. 2001 Oct;41(10):1091-7. doi: 10.1177/00912700122012698.