The effect of treatment with a new antidepressant, INN 00835, on platelet serotonin uptake in depressed patients

BACKGROUND: INN 00835 (4-fluoro-L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-arginyl-glycyl-trypt ophanamide ditrifluoroacetate) is a synthetic pentapeptide antidepressant with a potential for rapid onset of action. We were interested to see if such action could be correlated with serotonin uptake by platelets. METHODS: In a phase II clinical trial, unipolar depressed patients were administered active drug, INN 00835 or placebo, subcutaneously, at 0.2 mg/kg, once daily for 5 consecutive days. Efficacy of treatment was evaluated by psychometric tests (HAMD, MADS, CSRS, CGI and total VAS). Changes in platelet uptake rates of serotonin (3H-5HT) were measured in plasma from the patients participating in the phase II clinical trial, prior to and immediately after treatment with INN 00835 (19 patients) or placebo (16 patients), to evaluate the effect of treatment with INN 00835 on the rate of platelet 5-HT uptake. RESULTS: The data evaluated by using the psychometric tests indicated a significant response to treatment with INN 00835 after 5 days of dosing. The rates of platelet 5-HT uptake were lower prior to treatment (baseline), and increased after the 5-day treatment period. The change in the uptake rate (deltaVmax) following treatment was significantly larger in the active group than in the placebo group (P < 0.05). The difference between the placebo group and the patients who responded to treatment was even larger. LIMITATIONS: Small number of subjects. CONCLUSION: The data tend to substantiate the use of platelet serotonin uptake as a biochemical marker of effective treatment of depression.     

Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial

OBJECTIVE: Depression and hostility are significant risk factors for mortality and morbidity after myocardial infarction (MI). Much research is still needed to identify effective ways to reduce emotional distress in patients with cardiovascular disease. This double-blind, placebo-controlled study investigated the efficacy and safety of the antidepressant fluoxetine in patients with depression after their first MI. METHODS: Fifty-four patients with major depression after MI were randomly assigned to receive a flexible-dose regimen of fluoxetine or placebo for the first 9 weeks of a double-blind, placebo-controlled trial. Patients without serious adverse effects who wished to continue participating in the study were given fluoxetine or placebo for an additional 16 weeks. To evaluate the efficacy of fluoxetine, the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Hostility Scale of the 90-item Symptom Check List (SCL-90) were used as primary measures of outcome. To evaluate the safety of fluoxetine, cardiac function was measured before and after treatment with echocardiography and electrocardiography. RESULTS: The a priori difference in antidepressive efficacy (4-point difference in HAMD-17 scores between the fluoxetine and placebo groups) was not met. However, the response rate among patients receiving fluoxetine was significantly greater than that among patients receiving placebo at week 25 (48 vs. 26%, p = .05). Among patients with mild depression (HAMD-17 score < or =21), HAMD-17 scores were significantly different (p < .05) between the fluoxetine and placebo groups at weeks 9 (by 5.4 points) and 25 (by 5.8 points). Also, hostility scores at week 25 were significantly reduced among patients receiving fluoxetine (p = .02). Analysis of electrocardiographic and echocardiographic parameters revealed no decrease in cardiac function as a result of treatment with fluoxetine. Conclusions: Although the overall difference between the fluoxetine and placebo groups was not significant, there was a trend favoring fluoxetine in this relatively small sample. The response rate in the group receiving fluoxetine was comparable with that observed in other studies of patients with cardiovascular disease. In addition, fluoxetine seemed to be particularly effective in patients with mild depression and was associated with a statistically significant reduction in hostility. The results of this study suggest that fluoxetine can be safely used to treat patients with post-MI depression beginning 3 months after the event.     

The safety and efficacy of subcutaneous birch pollen immunotherapy - a one-year, randomised, double-blind, placebo-controlled study

BACKGROUND: There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America. METHODS: Thirty-five patients with severe rhinoconjunctivitis (hay fever) to birch pollen were allocated to double-blinded clustered IT with a depot birch pollen extract (Betula verrucosa) or placebo injections. Seven patients in each group had concomitant self-reported seasonal asthma. Treatment was conducted as a clustered regimen and was performed in a specialist unit. Symptom scores from nose, eyes, and lungs, and use of oral and topical antihistamines, beta-2-agonists, and oral corticosteroids were recorded daily during the season of 2000. Sensitivity to allergen provocation in skin, conjunctiva, and nasal mucosa was measured before and after 10 months of treatment. Post-seasonal assessment of symptom severity was performed using a simple questionnaire. RESULTS: IT reduced the symptom score for both rhinoconjunctivitis and asthma (P-values < 0.05), total medication score (P < 0.02) and use of oral antihistamines (P < 0.01). IT reduced specific conjunctival sensitivity (P < 0.05), skin prick test, and especially cutaneous late-phase response diameters (P < 0.00001), and increased general well-being on post-seasonal evaluation (P < 0.01). IT was safe, with side-effects at the same level as placebo. CONCLUSIONS: High-dose, subcutaneous IT is efficacious and safe in patients with severe birch pollen rhinoconjunctivitis and asthma.     

A double-blind,placebo-controlled study of sertraline in the prevention of depression in stroke patients

The authors tested the effect of sertraline in the prevention of poststroke depression. After experiencing an acute ischemic stroke, nondepressed patients (N=137) were randomly assigned to 12 months of double-blind treatment with either sertraline (N=70) or placebo (N=67). Kaplan-Meier analysis showed sertraline to have significantly superior prophylactic efficacy compared with placebo. Two definitions of clinical depression were used: total score >18 on the HAM-D(17) and score >or=9 on the HAM-D(6). Approximately 10% of the sertraline-treated group developed depression according to either definition, whereas 30% developed depression in the placebo group. On the HAM-D(6) the superiority of sertraline to placebo was demonstrated already after 6 weeks of therapy. Treatment was well tolerated; patients treated with sertraline experienced significantly fewer adverse events.     

Randomized, double-blind, parallel groups, placebo-controlled study of efficacy and safety of Rynatan in the treatment of allergic rhinitis using an acute model

We conducted a randomized, double-blind, parallel groups, placebo-controlled acute study of Rynatan (8 mg chlorpheniramine tannate, 25 mg pyrilamine tannate, 25 mg phenylephrine tannate) in 104 volunteers with allergic rhinitis. Subjects reported to City Park on a Saturday morning during the height of the grass pollen season in late spring and remained in the park for eight hours that day and on the following day. Cards were completed hourly to evaluate symptoms of allergic rhinitis and adverse experiences caused by therapy. The first three cards completed on Saturday morning were used to demonstrate that each subject had had at least minimal symptoms of allergic rhinitis and to determine baseline symptoms. Rynatan or placebo was given at noon and 7:30 PM that day and at 8:30 AM the next day. Subjects completed symptom cards hourly until 4:30 PM on Saturday, three cards that evening, and eight cards hourly the next day until 4:30 PM. The group receiving Rynatan had significantly more allergic rhinitis symptom relief than the placebo group (P = .003). More subjects in the Rynatan group (34/52) reported global symptom improvement than did subjects in the placebo group (18/52, P = .002). There were no significant severe adverse experiences and no statistically significant differences between treatment groups in incidence or severity of drowsiness, dizziness, jitteriness, headache, or nausea. We conclude that Rynatan is safe and effective in treating acute symptoms of allergic rhinitis in otherwise healthy adult subjects.     

A sham-controlled trial of the efficacy and safety of twice-daily rTMS in major depression

BACKGROUND: Studies of repetitive transcranial magnetic stimulation (rTMS) in depression have mostly involved once-daily treatment, with positive but modest clinical results. This study tested the efficacy and safety of twice-daily rTMS over 2 weeks. METHOD: Thirty-eight depressed subjects enrolled in a double-blind, sham-controlled trial of twice-daily rTMS (left prefrontal cortex, 10 Hz, 110% intensity, 1500 stimuli per session) over 2 weeks. Mood and neuropsychological functioning were assessed weekly by blind raters, using the Montgomery-Asberg Depression Rating Scale (MADRS) as the primary outcome measure, plus the Hamilton Rating Scale for Depression (HRSD) and self-report measures. After the blind period, 22 subjects continued with once-daily rTMS to receive a total of 6 weeks of active rTMS. RESULTS: Subjects were moderately treatment resistant. Active treatment resulted in significantly greater improvement than sham over the 2-week blind period on one outcome measure only (MADRS p<0.05). Subjects showed further improvement over the 6 weeks of active rTMS. Neuropsychological test scores did not change significantly. CONCLUSIONS: rTMS given twice daily was effective and safe, with no adverse neuropsychological effects.     

Hyperbaric-oxygen treatment of multiple sclerosis. A randomized, placebo-controlled, double-blind study

Several uncontrolled studies have suggested a beneficial effect of hyperbaric oxygen on multiple sclerosis. We studied 40 patients with advanced chronic multiple sclerosis who were randomly divided into two matching groups. The experimental group received pure oxygen, and the placebo group received a mixture of 10 per cent oxygen and 90 per cent nitrogen; both groups were treated at a pressure of 2 atmospheres absolute for 90 minutes once daily, for a total of 20 exposures. Objective improvement occurred in 12 of 17 patients treated with hyperbaric oxygen and in 1 of 20 patients treated with placebo (P less than 0.0001). Improvement was transient in seven of the patients treated with oxygen and long-lasting in five. Those with less severe forms of the disease had a more favorable and lasting response. At one year of follow-up, deterioration was noticed in 2 patients (12 per cent) in the oxygen group, neither of whom had had an initial response, and in 11 patients (55 per cent) in the placebo group, one of whom had had a positive initial response (P less than 0.0008). Minor ear problems and reversible myopia were the only side effects observed. These preliminary results suggest a positive, though transient, effect of hyperbaric oxygen on advanced multiple sclerosis, warranting further study. This therapy cannot be generally recommended without longer follow-up periods and additional confirmatory experience.     

A three-year double-blind placebo-controlled study with specific oral immunotherapy to Dermatophagoides: evidence of safety and efficacy in paediatric patients

Very few double-blind trials of oral immunotherapy have been reported. The majority of these have been performed with pollen extracts and the results have often been equivocal. The major weaknesses of these studies have been the short periods of the trials, the low doses of allergen employed and inadequate evaluation of efficacy. The present study has involved a placebo-controlled double-blind trial of oral immunotherapy for three years with Dermatophagoides pteronysstnus at relatively high doses in 18 paediatric patients. Throughout the trial clinical parameters (symptom and medication scores) and immunological parameters (specific IgE, IgG1 and IgG4 levels) were monitored in order to assess the safely and efficacy of the treatment. The treatment was well tolerated by all patients and no side-effects were experienced. Clinical improvement was evident after the second year of therapy and this was confirmed by a significant reduction in conjunctiva! reactivity assessed by a specific conjunctival provocation lest. In addition, there were significant changes in the immunological parameters with a reduction in specific IgE and increased levels of IgG4 and IgGI, results in keeping with previous studies of oral and subcutaneous immunotherapy. Although the results do not provide an explanation of the basis of successful oral immunotherapy, they clearly demonstrate the efficacy and safety of the treatment and suggest that it may be a useful and more acceptable alternative for patients than the traditional subcutaneous immunotherapy.     

Divalproex in the treatment of bipolar depression: a placebo-controlled study

BACKGROUND: The treatment of bipolar disorder in the depressed phase is complicated by a tendency for conventional antidepressant drugs to worsen the course of the illness by precipitating a manic episode or increasing cycle frequency. Thus, the potential antidepressant efficacy of mood stabilizers, such as divalproex, which is an effective treatment for the manic phase of bipolar disorder, is of considerable interest. METHODS: The clinical efficacy of divalproex (valproate, Depakote) was tested in an 8-week, double-blind, placebo-controlled, randomized clinical trial in 25 outpatients with bipolar I depression. The primary outcome measure was the 17-item Hamilton Rating Scale for Depression, and secondary measures included the Hamilton Rating Scale for Anxiety, the Clinician Administered Rating Scale for Mania, and the Clinical Global Impression scale. RESULTS: Using repeated measures ANOVA with last observation carried forward, divalproex was more effective than placebo in improving symptoms of depression (p = 0.0002) and symptoms of anxiety (p = 0.0001) than placebo. LIMITATIONS: The sample size was small, and most patients were male. CONCLUSIONS: These pilot results indicate that divalproex is effective in reducing the symptoms of depression and anxiety in bipolar I, depressed phase. These positive results support the need to perform a larger, multisite study of divalproex treatment for bipolar depression.     

Transdermal estradiol for postpartum depression: results from a pilot randomized,double-blind,placebo-controlled study

Archives of Women's Mental Health - Postpartum depression (PPD) is a common complication following delivery, though evidence-based treatment options are limited. This study explores the...     

Efficacy and safety of a soy isoflavone extract in postmenopausal women: a randomized, double-blind, and placebo-controlled study

OBJECTIVE: To investigate the efficacy of soy isoflavone on climacteric symptoms in postmenopausal women. DESIGN: In this double-blind, randomized, placebo-controlled study, a total of 80 women (mean age = 55.1 years), who reported 5 or more hot flush episodes per day, were randomized to receive either 250 mg of standardized soy extract (Glycine max AT) a total of 100mg/day of isoflavone (n = 40) or placebo (n = 40). Exclusion criteria included: contra-indication for hormone therapy (HT), chronic gastrointestinal diseases, and users of HT within the preceding 6-months. For 10-months, climacteric symptoms were evaluated using a score card and the menopausal Kupperman index. Compliance and safety were also assessed. At baseline and the end of the study, lipid and hormonal profiles, as well as vaginal, mammographic and ultrasonographic parameters were measured. The t-test, Wilcoxon test and ANOVA were used in the statistical analysis. RESULTS: At baseline, the mean number of hot flushes was 9.6 +/- 3.9 per day in the isoflavone group and 10.1+/-4.9 in the placebo group (p>0.05). After 10 months, there was a significant reduction in frequency of hot flushes among isoflavone users when compared to those on placebo (3.1 +/- 2.3 and 5.9 +/- 4.3, respectively) (p<0.001). Kupperman index mean values showed a significant reduction in both groups. However, soy isoflavone was significantly superior to placebo, in reducing hot flush severity (69.9% and 33.7%, respectively) (p<0.001). Endometrial thickness, mammography, vaginal cytology, lipids and hormonal profile did not change in both groups. No serious adverse event related to isoflavone treatment was reported. CONCLUSIONS: The soy isoflavone extract exerted favorable effects on vasomotor symptoms and good compliance, providing a safe and effective alternative therapeutic for postmenopausal women.     

Tryptophan and tyrosine availability and response to antidepressant treatment in major depression

BACKGROUND: It has been suggested that the ratio of tryptophan (TRP) and tyrosine (TYR) to other large neutral amino acids may predict response to antidepressant drugs with predominantly serotonergic compared with predominantly noradrenergic activity and that this may be clinically useful. METHOD: 147 subjects with a DSM-III-R diagnosis of major depression underwent a detailed clinical evaluation and prior to treatment had baseline measures of TRP, TYR and other large neutral amino acids (LNAA), prolactin and cortisol. Subjects entered a 6-week randomised treatment trial comparing fluoxetine and nortriptyline. RESULTS: There was no main effect on 6-week outcome of TRP/LNAA ratio or TYR/LNAA ratio and no interaction between these factors and treatment (fluoxetine vs nortriptyline). LIMITATIONS: Alterations in antidepressant dose were allowed therefore possibly reducing the effect of TRP or TYR availability on response. CONCLUSIONS: Previous findings that TRP/LNAA and TYR/LNAA ratios may predict differential response to antidepressants were not replicated and neither was our previous finding of a complex relationship between TRP/LNAA and baseline prolactin in predicting 6-week response.     

A double-blind comparative study of the safety and efficacy of caspofungin versus micafungin in the treatment of candidiasis and aspergillosis

The safety and efficacy profile of caspofungin and micafungin in Japanese patients with fungal infections were directly compared in this prospective, randomized, double-blind study. The proportion of patients who developed significant drug-related adverse event(s) (defined as a serious drug-related adverse event or a drug-related adverse event leading to study therapy discontinuation) was compared in 120 patients [caspofungin 50 mg, or 50 mg following a 70-mg loading dose on Day 1 (hereinafter, 70/50 mg) group: 60 patients; micafungin 150 mg: 60 patients]. The overall response rate was primarily evaluated in the per-protocol set (PPS) population. The proportion of patients who developed significant drug-related adverse events was 5.0 % (3/60) in the caspofungin group and 10.0 % (6/60) in the micafungin group [95 % confidence interval (CI) for the difference: ?15.9 %, 5.2 %]. The favorable overall response in the PPS population for patients with esophageal candidiasis, invasive candidiasis, and chronic pulmonary aspergillosis including aspergilloma was 100.0 % (6/6), 100.0 % (3/3), and 46.7 % (14/30) in the caspofungin group, and 83.3 % (5/6), 100.0 % (1/1), and 42.4 % (14/33) in the micafungin group, respectively. In Japanese patients with Candida or Aspergillus infections, there was no statistical difference in the safety between caspofungin and micafungin. Consistent with other data on these two agents, the efficacy of caspofungin and micafungin was similar.     

A double-blind, placebo-controlled study to assess the efficacy of nedocromil sodium in the management of childhood grass-pollen asthma

The aim of this double-blind placebo-controlled trial was to assess the efficacy and tolerance of nedocromil sodium at a dose of 4 mg four times daily, in the management of children suffering from grass-pollen asthma. Thirty-one children suffering from seasonal asthma (24 boys and seven girls, aged 4-21 yr, mean 11 yr) were enrolled in the study during the 1988 pollen season. Only one child was aged 4 yr, and she was a cooperative girl able to use the metered dose inhaler properly. In addition, in each group there was a patient aged 20 and 21 years, respectively, who had been followed up by us since childhood. Treatments were delivered by pressurized aerosol over a period of 4 weeks following a 1-week baseline, during which patients were required to show active disease by obtaining a minimum symptom score (almost 2 points of severity score on at least 3 days of the baseline period). The patients were randomly assigned to both treatment groups, all were taking inhaled or oral bronchodilators, when necessary. Twenty-nine patients completed the trial, 16 in the nedocromil sodium treatment group and 13 in the placebo group. One child of each group was withdrawn due to treatment failure. Statistically significant differences in favour of nedocromil sodium were found regarding morning tightness and mean morning PEFR values on diary cards (P less than 0.01 and P less than 0.05, respectively), bronchodilator usage (P less than 0.05), pulmonary function tests (PFT) at clinic visits (P less than 0.05), and in parents' opinion (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Targeting adenosine receptors in the treatment of allergic rhinitis: a randomized, double-blind, placebo-controlled study

BACKGROUND: There is evidence that adenosine plays a role in the pathogenesis of asthma and rhinitis; however, it is currently unclear whether adenosine receptors are useful therapeutic targets in the treatment of allergic airway diseases. OBJECTIVE: The study evaluated the efficacy of intranasal treatment with an adenosine A(2A) receptor agonist/adenosine A(3) receptor antagonist (50 micro g), administered twice daily for 7 days, to reduce nasal symptoms and release of inflammatory mediators following intranasal allergen challenge in patients with allergic rhinitis (AR). The compound was compared with twice-daily treatment with intranasal fluticasone proprionate nasal spray (FPANS) for 7 days. METHODS: A randomized, double-blind, double-dummy, placebo-controlled, three-way balanced, incomplete block, crossover study was conducted on 48 males with verified AR. Following intranasal challenge with either an extract from the house dust mite (HDM), Dermatophagoides pteronyssinus, rye grass or cat dander, nasal responses and the concentrations of albumin, tryptase, myeloperoxidase, eosinophilic cationic protein, epithelial neutrophil-activating protein-78 (ENA-78), IL-5 and IL-8 in nasal secretions were measured and treatment groups were compared. RESULTS: Drug improved nasal blockage but had no significant effect on rhinorrhoea, number of sneezes or peak nasal inspiratory flow measurements when compared with placebo. Drug reduced tryptase release after EAR but did not significantly reduce the levels of other mediators. CONCLUSION: A novel agonist/antagonist of adenosine A(2A) and A(3) receptors appears to have limited clinical benefit in both the early-phase and the late-phase response to intranasal allergen challenge. However, reduction of some pro-inflammatory mediators suggests that comparable, more selective compounds may have additional benefits meriting further investigation.     

Rupatadine in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled multicentre study

BACKGROUND: Chronic urticaria is one of the most common and disturbing cutaneous condition. The treatment of chronic idiopathic urticaria (CIU) is still a challenge. Antihistamines are recommended as first-line treatment. Rupatadine is a new potent nonsedative anti-H1. OBJECTIVE: To study rupatadine efficacy and safety for moderate to severe CIU treatment. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, multicentre, study was designed to assess primarily mean pruritus score (MPS) reduction with rupatadine, 10 and 20 mg, administered once daily for 4 weeks. Three hundred and thirty-three patients with active episodes of moderate-to-severe CIU were included. RESULTS: A 57.5% (P < 0.005) and 63.3% (P = 0.0001) significative MPS reduction from baseline, was observed at week 4 with 10 and 20 mg rupatadine, respectively, compared with placebo (44.9%). Both doses of rupatadine were not significantly different at any time point, with respect to their effects on pruritus severity, number of wheals and total symptoms scores. Rupatadine 10 mg had an overall better adverse event profile. CONCLUSION: Rupatadine 10 mg is a fast, long-acting, efficacious and safe treatment option for the management of patients with moderate-to-severe CIU.     

Oxandrolone in the treatment of HIV-associated weight loss in men: a randomized, double-blind, placebo-controlled study

OBJECTIVE: To evaluate the efficacy and safety of oxandrolone in promoting body weight and body cell mass (BCM) gain in HIV-associated weight loss. METHODS: Randomized, double-blind, placebo-controlled trial. Two hundred sixty-two HIV-infected men with documented 10% to 20% weight loss or body mass index < or =20 kg/m were randomized to placebo or to 20, 40, or 80 mg of oxandrolone daily. After 12 weeks, subjects were allowed to receive open-label oxandrolone at a dose of 20 mg for another 12 weeks. RESULTS: Body weight increased in all groups, including the group receiving placebo, during the double-blind phase (1.1 +/- 2.7, 1.8 +/- 3.9, 2.8 +/- 3.3, and 2.3 +/- 2.9 kg in placebo and 20-, 40-, and 80-mg oxandrolone groups, respectively; all P < 0.014 vs. baseline). BCM increased from baseline in all groups (0.45 +/- 1.7, 0.91 +/- 2.2, 1.5 +/- 2.5, and 1.8 +/- 1.8 kg in placebo and 20-, 40-, and 80-mg oxandrolone groups, respectively). At 12 weeks, only the gain in weight at the 40-mg dose of oxandrolone and the gain in BCM at the 40- and 80-mg doses of oxandrolone were greater than those in the placebo group, however. Oxandrolone treatment was associated with significant suppression of sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone, and total and free testosterone levels. Treatment was generally well tolerated but accompanied by significant increases in transaminases and low-density lipoprotein as well as decreases in high-density lipoprotein. CONCLUSION: Oxandrolone administration is effective in promoting dose-dependent gains in body weight and BCM in HIV-infected men with weight loss.     

Wheat allergy: a double-blind, placebo-controlled study in adults

BACKGROUND: Wheat is believed to be an uncommon cause of food allergy in adults; the number of studies that address IgE mediated wheat allergy in adults is all too few. OBJECTIVE: Determine how many subjects with a history of wheat allergy have real allergy by double-blind, placebo-controlled food challenge; identify the symptoms manifested during the challenge; determine the lowest provocation dose; determine the performance characteristics of wheat skin prick test and specific IgE; identify subjects with real wheat allergy for potential immunoblotting studies. METHODS: Patients underwent skin test with commercial wheat extract; specific wheat IgE was determined. Subjects were challenged with 25 g wheat. Subjects who were positive to raw wheat challenge underwent cooked wheat challenge. RESULTS: Thirty-seven double-blind placebo-controlled wheat challenges were performed on 27 patients. A total of 13 of 27 (48%) patients had a positive result. Eleven subjects with positive raw wheat challenge underwent cooked wheat challenge: 10 were positive. The provocation dose range was 0.1 to 25 g. Twenty-seven percent of the subjects allergic to wheat had a provocation dose that was < or =1.6 g. CONCLUSION: Wheat causes real food allergy in adults. More than a quarter of the patients allergic to wheat reacted to less than 1.6 g wheat. Specific IgE was more sensitive than skin test for wheat; however, specificity and predictive values were low for both tests. Thus, these tests should not be used to validate diagnosis of wheat allergy.