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

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00000790
• Collaborator: Andrulis Pharmaceuticals (Industry)
• Enrollment: 164
• Locations: 40
• Patients Per Site: 4.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Stomatitis, Aphthous	Drug: Thalidomide	Phase 2

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.

Study Design

• Study Type: Interventional
• Intervention Model: Parallel Assignment
• Primary Purpose: Treatment
• Official Title: Thalidomide for Treatment of Oral and Esophageal Aphthous Ulcers and HIV Viremia in Patients With HIV Infection
• Actual Study Completion Date: Oct 1, 1998

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California	United States	900331079
3	San Francisco AIDS Clinic / San Francisco Gen Hosp	San Francisco	California	United States	941102859
4	Stanford at Kaiser / Kaiser Permanente Med Ctr	San Francisco	California	United States	94115
5	Harbor UCLA Med Ctr	Torrance	California	United States	90502
6	Univ of Colorado Health Sciences Ctr	Denver	Colorado	United States	80262
7	Howard Univ	Washington	District of Columbia	United States	20059
8	Univ of Miami School of Medicine	Miami	Florida	United States	331361013
9	Queens Med Ctr	Honolulu	Hawaii	United States	96816
10	Univ of Hawaii	Honolulu	Hawaii	United States	96816
11	Northwestern Univ Med School	Chicago	Illinois	United States	60611
12	Cook County Hosp	Chicago	Illinois	United States	60612
13	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois	United States	60612
14	Louis A Weiss Memorial Hosp	Chicago	Illinois	United States	60640
15	Illinois Masonic Med Ctr	Chicago	Illinois	United States	606575147
16	Indiana Univ Hosp	Indianapolis	Indiana	United States	462025250
17	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts	United States	02114
18	Beth Israel Deaconess - West Campus	Boston	Massachusetts	United States	02215
19	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York	United States	10461
20	Comprehensive Health Care Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10461
21	Montefiore Adolescent AIDS Prog / Bronx Municipal Hosp	Bronx	New York	United States	10461
22	Montefiore Drug Treatment Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10461
23	Montefiore Family Health Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10461
24	Jack Weiler Hosp / Bronx Municipal Hosp	Bronx	New York	United States	10465
25	Montefiore Med Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10467
26	North Central Bronx Hosp / Bronx Municipal Hosp	Bronx	New York	United States	10467
27	Bronx Veterans Administration / Mount Sinai Hosp	Bronx	New York	United States	10468
28	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York	United States	14215
29	Beth Israel Med Ctr	New York	New York	United States	10003
30	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
31	Mount Sinai Med Ctr / Pediatrics	New York	New York	United States	10029
32	Mount Sinai Med Ctr	New York	New York	United States	10029
33	SUNY / State Univ of New York	Syracuse	New York	United States	13210
34	Univ of North Carolina	Chapel Hill	North Carolina	United States	275997215
35	Case Western Reserve Univ	Cleveland	Ohio	United States	44106
36	Milton S Hershey Med Ctr	Hershey	Pennsylvania	United States	170330850
37	Thomas Jefferson Univ Hosp	Philadelphia	Pennsylvania	United States	191075098
38	Meharry Med College	Nashville	Tennessee	United States	37203
39	Univ of Washington	Seattle	Washington	United States	981224304
40	Univ of Puerto Rico	San Juan		Puerto Rico	009365067

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Andrulis Pharmaceuticals

Investigators

• Study Chair: Jacobson JM,

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• Gilden D. Thalidomide and aphthous ulcers. GMHC Treat Issues. 1995 Nov;9(11):12.
• 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.
• 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.
• 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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00000790
• Other Study ID Numbers: ACTG 251; 11228
• First Posted: Aug 31, 2001
• Last Update Posted: Nov 4, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Thalidomide; Stomatitis, Aphthous
• Additional relevant MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Viremia; Stomatitis; Stomatitis, Aphthous; Thalidomide

Study Results

No Results Posted as of Nov 4, 2021