Seyed Ali Ahmad’s research while affiliated with University of California, Berkeley and other places

The purpose of this placebo-controlled, double-blind study was to determine the safety, tolerability and clinical efficacy of 5-fluorouracil (1%) in a vaginal hydrophilic gel (hydroxyethylcellulose, 1%) to cure intravaginal papillomas in women. Pre-selected, 60 women ranging between 18 and 50 years of age (mean 24.6), having 312 vaginal condylomas (mean 5.2) joined the study. The diagnosis of human papillomavirus (HPV) was established with clinical, histopathological and polymerase chain reaction (PCR) techniques. Subjects were randomized into 2 parallel groups. Each patient was allocated a pre-coded tube 15 g (active or placebo) with graduated vaginal applicators (disposable), and instructions how to insert 4 g of the trial medication deep into the vagina once at bedtime on every other day (1, 3 and 5) per week, to visit the clinic on day 7 for clinical evaluations and to receive the same pre-coded replacement to continue the regimen for another week. A maximum 12 applications were to be used in 4 weeks. Cure was defined as absence of clinical signs of infection, re-confirmed by PCR and Southern blot hybridization negative HPV DNA. By the end of the treatment 48.4% patients and 51.9% lesions were cured. Breaking the code revealed that 5-fluorouracil (1%) gel had cured 83.3% patients and 87% intravaginal warts. Placebo resolved 13.3% patients and 14% condylomas; (active gel versus placebo; P < 0.001). Twelve patients (20%) mostly in the active gel experienced mild erythema, erosion and oedema, with no drop-outs. Among cured patients 3 had a relapse after 16 months. In conclusion, the clinical results of the study demonstrate that 5-fluorouracil (1%) in a vaginal hydrophilic gel is safe, tolerable and significantly more effective than placebo to cure intravaginal warts in women.

Objective: To compare the clinical efficacy and tolerability of butenafine 1% in cream with terbinafine 1% in cream in the treatment of plantar or moccasin-type tinea pedis (athlete’s foot). Design and Setting: This was a placebo-controlled, double-blind study. Patients and Participants: 60 men aged between 18 and 60 years (mean 35.4 years) with a mean duration of disease of 28.4 weeks, positive mycology and culture-confirmed tinea pedis participated in the study. Methods: The participants were sequentially randomised into three parallel groups (butenafine cream, terbinafine cream and placebo). Each patient was given a precoded 25g tube and instructed to apply the trial medication to all tinea pedis lesions once daily at bedtime for 5 consecutive days per week (maximum of 2 weeks’ active treatment). Patients were examined on a weekly basis. Cure was defined as negative potassium hydroxide test results and negative fungal culture (mycological cure). Participants cured during the treatment were allowed to discontinue the treatment. Results: By the end of the treatment 60% of all patients were cured. Butenafine cured 18 (90%) patients at 1 week and no further patients at 2 weeks. Terbinafine cured no patients at 1 week and 16 (80%) patients at 2 weeks. Placebo cured no patients at 1 week and 2 (10%) patients at 2 weeks (p < 0.0001, butenafine and terbinafine vs placebo at 2 weeks). None of the patients reported any drug-related adverse events and no patients discontinued treatment. Conclusion: Butenafine 1% in cream is well tolerated and comparatively better than terbinafine 1% in cream or placebo to cure plantar or moccasin-type tinea pedis in men. Further clinical studies appear warranted.

Onychomycosis is an increasingly common and recalcitrant fungal nail infection world-wide. The purpose of this placebo-controlled, double-blind study was to determine the clinical efficacy, chemical avulsion, and tolerability of 2% butenafine hydrochloride and 20% urea incorporated in a cream to cure toenail onychomycosis in a preselected population. Sixty patients (38M, 22F), ranging between 18 and 60 years (mean 27.4), with more than 25% involvement of the big toenail were enrolled in the study. The diagnosis of onychomycosis was established by mycologic identification and reconfirmed by positive fungal culture. A precoded 25-g tube was randomly assigned to each patient (50 active and 10 placebo) with instructions to apply the trial medication to their infected toenail twice daily with an occlusive dressing for one week. The affected nail was removed with a nail clipper. No occlusive dressing was maintained after the initial one week regimen. To assess the chemical avulsion of the infected toenail, mycologic cure, clinical effectiveness of the treatment, and overall success, patients were examined twice a week for 16 weeks and thereafter on a weekly basis for a further 36 weeks. The treatment was well tolerated by all the patients throughout the study, with no dropouts. Marked improvement was seen in 73.3% patients after weeks 8, 16 and 24 with clinically and mycologically confirmed negative fungal culture. Code disclosure revealed that active butenafine and urea cream cured significantly more patients than placebo (88% versus 0%; p < 0.0001). Of the 60 patients 91.6% reported no drug-related adverse symptoms. Five patients reported non-objective mild inflammation without discontinuation of the treatment. During one year follow-up of the study phase, none of the cured patients had a relapse. In conclusion, the mycologic and overall assessment of this study demonstrate that 2% butenafine HCl and 20% urea incorporated in a cream for keratinolysis is safe to use and significantly more effective than placebo in curing big toenail onychomycosis.

The aim of this randomised, double-blind, placebo-controlled study was to examine the clinical significance, efficacy and tolerability of imiquimod 1% cream to manage patients exposed to first episodes of genital herpes. Male patients (n = 60), ranging in age between 18 and 50 years (mean 25.7 years), presenting for <6 days (mean 4.4 days) with culture-confirmed diagnosis of genital herpes, and bearing a total of 696 lesions (mean 11.6 lesions/ patient), entered the study and were randomised to receive a precoded 40g tube and instructions on how to apply the trial medication to their lesions twice for 5 consecutive days per week. A marked clinical benefit from self-application of imiquimod 1% cream was demonstrated, resulting in both significantly shorter mean duration of healing than with the placebo (5.2 vs 14 days; p < 0.001) and more healed patients [23 of 30 (76.7%) vs 2 of 30 (6.7%); p < 0.0001]. Of the 60 patients, 54 (90%) reported no drug-related adverse effects. Two patients in the imiquimod group reported non-objective mild burning sensation and four experienced a transitory increase in their body temperature (>38 degrees C) accompanied by mild headache and malaise; however, such indications were not severe enough to cause discontinuation of the treatment, and resolved within 24 hours. Treatment was well tolerated by all the patients, with no dropouts. Among 25 healed patients, four had a relapse after 9 months. Although the analogue of imiquimod 1% cream demonstrated mild to moderate subjective adverse effects, it was significantly more effective than placebo in treating patients with a first episode of genital herpes. Further clinical studies appear warranted.

The purpose of this randomized, double-blind, placebo-controlled study was to determine the clinical efficacy and tolerability of an analog of imiquimod (2%)in cream to cure genital warts in women. Sixty preselected women, ranging between 18 and 45 years of age (mean 24.3) and having 411 lesions (mean 6.8) with clinical, histopathological and polymerase chain reaction (PCR) confirmed diagnosis of human papilloma virus (HPV) infection were randomized to two parallel groups. Each patient received a precoded 40-g tube and instructions on how to apply the trial medication to their lesions at home two times daily for five consecutive days per week. The active treatment period was six weeks. Patients were evaluated on a weekly basis. A clinically and PCR established total clearance of target warts was recorded as a cure. By the end of the treatment, 43.3% of patients and 42.8% of warts were cured. Code disclosure revealed that imiquimod cream had cured 83.3% of the treated patients and 84.3% of the tested warts, while the placebo healed one subject and four warts (p < 0.0001). Eight patients (13.3%) in the imiquimod group experienced mild to moderate, non-objective, drug-induced symptoms with no dropouts. Among the 26 cured patients, five had a relapse after 11 months. In conclusion, the data presented demonstrate that 2% imiquimod in cream with mild to moderate subjective side effects is significantly more effective than placebo in eliminating genital warts in women.

The objective of this double-blind, placebo-controlled study was to evaluate in males the clinical efficacy in treating molluscum contagiosum and tolerance of an analog of imiquimod (1%) in cream. One hundred patients between 9 and 27 years of age (mean 16.3), with 733 lesions (mean 7.3), whose size ranged from 2 to 5 mm diameter (mean spot size 3.4 mm) and a biopsy-confirmed diagnosis of molluscum contagiosum were randomized into two parallel groups. In a double-blind manner, precoded 40-g tubes were dispensed. Patients self-administered the trial medication to their lesions at home three times daily for five consecutive days per week. The study was scheduled with 4 weeks of active treatment (maximum 60 topical applications) and 12 months (on a monthly basis) of follow-up. Patients were examined on a weekly basis. Thirteen patients had atopic dermatitis. A clinically and histopathologically confirmed total elimination of lesions was considered as cured. After four weeks of treatment, 49 patients and 372 lesions were cured. Breaking the code revealed that imiquimod cream had cured 82% of the patients and 86.3% of the lesions. Placebo cleared 16% of the patients and 63 of the lesions (p < 0.0001). During the treatment, 88% of the patients experienced no allergic, localized, or drug-related adverse symptoms. Twelve patients, predominantly in the imiquimod cream group reported non-objective, drug-induced, mild reactions with no dropouts. The study was followed-up for 12 months. Among 49 cured patients, 3 had relapses after 10 months. In conclusion, the study demonstrated that 1% imiquimod analog in cream with mild subjective side effects is significantly more efficacious than the placebo in curing molluscum contagiosum in males.

The aim of this double‐blind, placebo‐controlled, comparative study was to differentiate the clinical efficacy and tolerability of human leukocyte interferon‐α incorporated (2 times 10 ⁶ IU/g) in a hydrophilic cream and in a gel to heal males afflicted with first episodes of genital herpes. Patients (n=60), aged 18–40 years (mean 23.2) with culture‐confirmed diagnosis of herpes genitalis were randomized to three parallel groups. Each patient was allocated a precoded 40‐g tube, containing either preparation or placebo. Cream or gel was applied three times daily for 5 consecutive days. The duration of the active treatment was two weeks. Patients were examined after 48 hours of initial treatment, and thereafter two times a week. A reepithelialized lesion with some residual erythema was recorded as healed. The study demonstrated that patients treated with leukocyte interferon‐α cream had both significantly shorter mean duration of lesions than gel and placebo recipients (5.3 days vs. 8 days, 13 days respectively; p<0.001) and a higher number of healed patients (80% vs. 55%, 20% respectively; p<0.001). Of the 60 patients, 49 (82%) complained of no drug‐related side effects. Eleven patients predominantly in the cream/gel groups reported non‐objective transitory increase in their body temperature (>38°C) with moderate headache, malaise and myalgia. The study was followed‐up for 24 months after the first day of the treatment, and out of 31/60 cured patients, 4 had a relapse after 18 months. In conlusion the study affirmed that human leukocyte interferon‐α (2 times 10 ⁶ IU/g) in a hydrophilic cream is more efficacious than its incorporation in gel or placebo, thus suggesting that leukocyte interferon‐α in a hydrophilic cream, with a profile of non‐objective mild to moderate drug‐induced indications, may be considered an alternative and effective treatment modality to cure male patients afflicated with first episodes of genital herpes.

The purpose of this double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerability of topical Aloe vera extract 0.5% in a hydrophilic cream to cure patients with psoriasis vulgaris. Sixty patients (36M/24F) aged 18–50 years (mean 25.6) with slight to moderate chronic plaque-type psoriasis and PASI (Psoriasis Area and Severity Index) scores between 4.8 and 16.7 (mean 9.3) were enrolled and randomized to two parallel groups. The mean duration of the disease prior to enrolment was 8.5 years (range 1–21). Patients were provided with a precoded 100 g tube, placebo or active (with 0.5%Aloe vera extract), and they self-administered trial medication topically (without occlusion) at home 3 times daily for 5 consecutive days per week (maximum 4 weeks active treatment). Patients were examined on a weekly basis and those showing a progressive reduction of lesions, desquamation followed by decreased erythema, infiltration and lowered PASI score were considered healed. The study was scheduled for 16 weeks with 12 months of follow-up on a monthly basis. The treatment was well tolerated by all the patients, with no adverse drug-related symptoms and no dropouts. By the end of the study, the Aloe vera extract cream had cured 25/30 patients (83.3%) compared to the placebo cure rate of 2/30 (6.6%) (P<0.001) resulting in significant clearing of the psoriatic plaques (328/396 (82.8%) vs placebo 28/366 (7.7%), P<0.001) and a decreased PASI score to a mean of 2.2. The findings of this study suggest that topically applied Aloe vera extract 0.5% in a hydrophilic cream is more effective than placebo, and has not shown toxic or any other objective side-effects. Therefore, the regimen can be considered a safe and alternative treatment to cure patients suffering from psoriasis.