Michel A. Drouin

The monosodium glutamate symptom complex: Assessment in a double-blind, placebo-controlled, randomized study

BACKGROUND Considerable debate swirls about the validity of symptoms described by many people after ingestion of monosodium glutamate (MSG), and the question has remained unresolved largely because of a paucity of well-designed challenge studies. METHODS We conducted oral challenge studies in self-identified MSG-sensitive subjects to determine whether they had a statistically significant difference in the incidence of their specific symptoms after ingestion of MSG compared with placebo. First, 5 gm MSG or placebo was administered in random sequence in a double-blind fashion. Subjects who reacted only to a single test agent then underwent rechallenge in random sequence in a double-blind fashion with placebo and 1.25, 2.5, and 5 gm MSG. A positive response to challenge was defined as the reproduction of > of 2 of the specific symptoms in a subject ascertained on prechallenge interview. RESULTS Sixty-one subjects entered the study. On initial challenge, 18 (29.5%) responded to neither MSG nor placebo, 6 (9.8%) to both, 15 (24.6%) to placebo, and 22 (36.1%) to MSG (p = 0.324). Total and average severity of symptoms after ingestion of MSG (374 and 80) were greater than respective values after placebo ingestion (232 and 56; p = 0.026 and 0.018, respectively). Rechallenge revealed an apparent threshold dose for reactivity of 2.5 gm MSG. Headache (p < 0.023), muscle tightness (p < 0.004), numbness/tingling (p < 0.007), general weakness (p < 0.040), and flushing (p < 0.016) occurred more frequently after MSG than placebo ingestion. CONCLUSIONS Oral challenge with MSG reproduced symptoms in alleged sensitive persons. The mechanism of the reaction remains unknown, but symptom characteristics do not support an IgE-mediated mechanism. According to Food and Drug Administration recommendations, the symptoms, originally called the Chinese restaurant syndrome, are better referred to as the MSG symptom complex.

Once daily mometasone furoate aqueous nasal spray is as effective as twice daily beclomethasone dipropionate for treating perennial allergic rhinitis patients

BACKGROUND Perennial allergic rhinitis is chronic and persistent, may lead to a constellation of secondary complaints including sinusitis, mouth-breathing, and some symptoms resembling a permanent cold, and often requires constant medical intervention. Well-tolerated nasal corticosteroids, alone or in combination with antihistamines, have been found to be very effective in treating this condition. OBJECTIVE To compare the effectiveness and tolerability of mometasone furoate aqueous suspension, a new once daily nasal spray, to placebo vehicle and to beclomethasone dipropionate, administered twice daily, in patients with perennial allergic rhinitis. METHODS This was a randomized, double-blind, placebo-controlled, double-dummy, parallel group study, in 427 patients age 12 years and older at 24 centers in Canada and Europe. Patients allergic to at least one perennial allergen, confirmed by medical history, skin testing, and adequate symptomatology were eligible to receive one of the following regimens for 3 months: mometasone furoate, 200 micrograms only daily; beclomethasone dipropionate, 200 micrograms twice daily (400 micrograms total dose); or placebo vehicle control. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment. RESULTS Three hundred eighty-seven patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < or = .01) more effective than placebo and was indistinguishable from beclomethasone dipropionate. Similar trends were seen among individual symptoms, physician symptom evaluations, and therapeutic response. There was no evidence of tachyphylaxis. All treatments were well tolerated. CONCLUSIONS Mometasone furoate nasal spray adequately controls symptoms of perennial allergic rhinitis, offers the advantage of once daily treatment, and is well tolerated.

Intranasal fluticasone propionate versus loratadine in the treatment of adolescent patients with seasonal allergic rhinitis

Fluticasone propionate (FP) is a topical corticosteroid with minimal systemic activity. We examined safety and compared the efficacy of FP aqueous nasal spray, 200 micrograms every day with loratadine tablets, 10 mg by mouth every day in 240 adolescents with ragweed pollen-induced seasonal allergic rhinitis for 4 weeks in a randomized, double-blind, parallel-group study. Nasal and eye symptoms were recorded daily on a 4-point (0 to 3) scale. A higher percentage of symptom-free days was observed for nasal blockage on waking during treatment with FP (p < 0.0001). Significant results were also obtained for all other nasal symptoms when analyzed for both symptom-free days and symptom scores. No differences were found for eye irritation symptoms (p = 0.14). Morning and evening nasal peak inspiratory flow (PIF) was recorded daily by 57 subjects. FP treatment was associated wit significantly higher PIF values than loratadine both morning (p = 0.0051) and evening (p = 0.0036). A greater improvement over 4 weeks was observed for PIF morning values in the FP group (p = 0.008) but not for evening values (p = 0.358). Statistically significant correlations were found for nasal blockage and PIF in the morning (r = -0.54, p = 0.0001) and in the evening (r = -0.46, p = 0.008).

Aspartame is no more likely than placebo to cause urticaria/angioedema: Results of a multicenter, randomized, double-blind, placebo-controlled, crossover study

BACKGROUND Anecdotes and single case reports have suggested that the high-intensity sweetener, aspartame, may be associated with allergic/hypersensitivity-type reactions. METHODS We conducted a multicenter, placebo-controlled clinical study to evaluate individuals who had experienced urticaria and/or angioedema allegedly associated with ingestion of an aspartame-containing product. Despite extensive recruiting efforts over 4 years, only 21 subjects could be enrolled. After admission to clinical research units, subjects were given aspartame and placebo in a randomized, double-blind, crossover fashion. Subjects received, on different days, increasing doses (50, 300, 600 mg) of aspartame and placebo at 8:00 AM, 10:00 AM, and noon. Subjects who weighed less than 40 kg received one half of these doses. Conversion products of aspartame, aspartyl-phenylalanine diketopiperazine and beta-aspartame, were also included in the aspartame arm of the study. Positive reactions were defined as urticaria (hives with wheals 4 mm or more in diameter with a collective diameter of at least 15 mm or one or more hives with a wheal of 4 mm or greater with a flare of 8 mm or greater) or as angioedema. RESULTS According to these criteria, four reactions were observed; two followed aspartame ingestion and two followed placebo ingestion (p = 1.00). The incidence of other adverse experiences was no different after aspartame versus placebo ingestion (p = 0.289). CONCLUSION These results indicate that aspartame and its conversion products are no more likely than placebo to cause urticaria and/or angioedema reactions in subjects with a history consistent with hypersensitivity to aspartame.

Budesonide aqueous nasal spray and pressurized metered dose inhaler in the treatment of adult patients with seasonal allergic rhinitis.

Budesonide, a topical corticosteroid used in the treatment of seasonal allergic rhinitis, can be administered to the nose as an aerosol via a pressurized metered dose inhaler (pMDI) or as a metered nasal pump spray. Studies have shown that about 64% (256 μg) of a nominal dose of 400 μg budesonide pMDI preparation is delivered to the patient compared with 100% of the nominal dose of the pump spray. The present study was undertaken to assess the efficacy and safety of budesonide delivered via a nasal pMDI twice daily (Rhinocort® pMDI, at 400 μg/day) with an aqueous suspension of budesonide delivered via a metered nasal pump spray once daily (Rhinocort® Aqua, at 256 μg/day or 400 μg/day). The multicenter, double-blind, randomized, placebo-controlled, parallel-group study was conducted in 318 patients (154 men, 164 women; aged 12–67 years) with ragweed-induced seasonal allergic rhinitis. A 1-week baseline period was followed by a 3-week treatment. Nasal symptoms were recorded by the patients, adverse events were noted, an overall evaluation of treatment efficacy was made, and urine cortisol and creatinine levels were measured. Substantial or total control of symptoms was achieved in 83.8% of patients treated with 256 μg of aqueous budesonide, 76.3% with 400 μg of aqueous budesonide, and 80.8% with 400 μg of budesonide pMDI; these were all significantly different (p < 0.001) compared with placebo (23.4% of patients). There were no significant differences in the 24-hour urine cortisol levels between the groups and there were few, infrequent adverse events, similar between the groups and resolved completely on discontinuation of treatment. It was concluded that budesonide, given once daily as 256 μg or 400 μg in an aqueous suspension or twice daily as 400 μg in a pMDI provides good alleviation of the symptoms of seasonal allergic rhinitis with no significant risk of suppression of urine cortisol.

Clinical evaluation of the efficacy and safety of noberastine, a new H1 antagonist, in seasonal allergic rhinitis: A placebo-controlled, dose-response study☆

Noberastine (NOB), a new histamine H1 antagonist, has potent and specific peripheral antihistaminic activity. To evaluate the efficacy and safety of NOB in ragweed seasonal allergic rhinitis, 250 eligible patients were randomized to one of four parallel, double-blind treatment groups: NOB, 10, 20, and 30 mg, or placebo, each administered once daily for 3 weeks. Rescue medication was prohibited. Efficacy parameters included global response rate (percentage of responders), physician visit, patient-diary symptom scores, and onset of action. Efficacy analyses used alpha = 0.0167 (adjusted for multiple comparisons). Efficacy parameters demonstrated universal superiority of NOB therapy over placebo therapy with statistical significance achieved frequently; no statistically or clinically significant separation was demonstrated among NOB-treated groups. Global-response rates for all active-treatment groups (range, 62.7% to 71.1%) were statistically significantly greater than rates for the placebo-treated group (39.6%). Median time to first relief of symptoms was within 2 to 4 hours for NOB-treated groups versus 72 hours for the placebo-treated group. No significant abnormalities in safety parameters were ascribed to NOB treatment. Incidence and severity of adverse experiences of NOB-treated groups were comparable in incidence and severity to placebo treatment. NOB treatment did not appear to cause weight gain or sedation. Once-daily NOB, 10, 20, and 30 mg, is equally and highly effective and safe in the symptomatic management of seasonal allergic rhinitis compared to placebo.

Faster onset of action with topical levocabastine than with oral cetirizine

This international multicentre, open-label, parallel-group trial was undertaken to compare the therapeutic efficacy and tolerability of topical levocabastine and oral cetirizine in patients with perennial allergic rhinoconjunctivitis, with particular reference to the comparative onset of action of the two drugs. A total of 207 patients were randomized to receive either levocabastine nasal spray (0.5 mg/ml, two sprays in each nostril twice daily) plus levocabastine eye drops as required (0.5 mg/ml, one drop in each eye twice daily p.r.n.) or cetirizine orally (10 mg once daily) with a treatment duration of 2 weeks. Onset of action was found to be significantly more rapid with levocabastine than with cetirizine for both nasal and ocular symptoms (p < 0.001). Within 15 min of study drug administration, 36% of levocabastine-treated patients reported relief from nasal symptoms and 32% relief from ocular symptoms compared with 10% and 17% of patients on cetirizine, respectively. At 1 h, the percentages of patients reporting relief were 76% and 38% for nasal symptoms, and 81% and 48% for ocular symptoms in the levocabastine and cetirizine treatment groups, respectively. At 8 h there were no differences between the two treatments. Overall therapeutic efficacy was found to be comparable in the two treatment groups over the 2-week study period with no significant intergroup differences in symptom severity or global therapeutic efficacy. Both drugs were well tolerated with no significant differences in the incidence or type of adverse reactions between the two groups. In conclusion, levocabastine eye drops and nasal spray are as effective and well tolerated as oral cetirizine for the treatment of perennial allergic rhinoconjunctivitis with the advantage of a significantly faster onset of action for both nasal and ocular symptoms.

Loratadine and Pseudoephedrine Sulfate: A Double-Blind, Placebo-Controlled Comparison of a Combination Tablet (SCH 434) and Its Individual Components in Seasonal Allergic Rhinitis

SCH 434 is a combination tablet containing the nonsedating antihistamine, loratadine (5 mg), and the well-established nasal decongestant, pseudoephedrine sulfate (120 mg), for twice daily dosing. The efficacy and safety of SCH 434 was compared with its individual components in a 14-day, placebocontrolled, randomized, double-blind, parallel-group, multi-center study in the symptomatic treatment of seasonal allergic rhinitis; 437 patients were evaluated for safety, 417 of whom were also evaluated for efficacy. Throughout the study, SCH 434 provided a significantly greater degree of overall symptom relief than either component alone or placebo. Loratadine alone was also superior to placebo on day 4 and at end point and superior to pseudoephedrine alone on day 4 in decreasing total symptom score. All treatments were well tolerated and no serious or unusual adverse experiences were reported; adverse experiences associated with SCH 434 were typical of the side effects commonly associated with the use of pseudoephedrine. The combination provides for a safe, effective, and convenient alternative for patients requiring the benefits of both an antihistamine and nasal decongestant, but who cannot tolerate, or wish to avoid, the sedative effects of traditional antihistamines.