Thalidomide for Treatment of Oral and Esophageal Aphthous Ulcers and HIV Viremia in Patients With HIV Infection

HIV Infections Clinical Trial

Official title:

Thalidomide for Treatment of Oral and Esophageal Aphthous Ulcers and HIV Viremia in Patients With HIV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000790
• Other study ID #: ACTG 251
• Secondary ID: 11228
• Status: Completed
• Phase: Phase 2
• Est. completion date: October 1998

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: October 1998
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• Infections
• Stomatitis
• Stomatitis, Aphthous
• Viremia

Intervention

Drug:
• Thalidomide

Locations

Country	Name	City	State
Puerto Rico	Univ of Puerto Rico	San Juan
United States	Univ of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess - West Campus	Boston	Massachusetts
United States	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts
United States	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York
United States	Bronx Veterans Administration / Mount Sinai Hosp	Bronx	New York
United States	Comprehensive Health Care Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Jack Weiler Hosp / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Adolescent AIDS Prog / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Drug Treatment Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Family Health Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Med Ctr / Bronx Municipal Hosp	Bronx	New York
United States	North Central Bronx Hosp / Bronx Municipal Hosp	Bronx	New York
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Cook County Hosp	Chicago	Illinois
United States	Illinois Masonic Med Ctr	Chicago	Illinois
United States	Louis A Weiss Memorial Hosp	Chicago	Illinois
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois
United States	Case Western Reserve Univ	Cleveland	Ohio
United States	Univ of Colorado Health Sciences Ctr	Denver	Colorado
United States	Milton S Hershey Med Ctr	Hershey	Pennsylvania
United States	Queens Med Ctr	Honolulu	Hawaii
United States	Univ of Hawaii	Honolulu	Hawaii
United States	Indiana Univ Hosp	Indianapolis	Indiana
United States	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California
United States	Univ of Miami School of Medicine	Miami	Florida
United States	Meharry Med College	Nashville	Tennessee
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Mount Sinai Med Ctr / Pediatrics	New York	New York
United States	Thomas Jefferson Univ Hosp	Philadelphia	Pennsylvania
United States	San Francisco AIDS Clinic / San Francisco Gen Hosp	San Francisco	California
United States	Stanford at Kaiser / Kaiser Permanente Med Ctr	San Francisco	California
United States	Univ of Washington	Seattle	Washington
United States	SUNY / State Univ of New York	Syracuse	New York
United States	Harbor UCLA Med Ctr	Torrance	California
United States	Howard Univ	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Andrulis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (5)

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. — View Citation

Gilden D. Thalidomide and aphthous ulcers. GMHC Treat Issues. 1995 Nov;9(11):12. — View 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. Epub 2000 Dec 15. — View 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. — View 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. — View Citation