A novel nonsurgical therapy for peri-implantitis using focused pulsed electromagnetic field: A pilot randomized double-blind controlled clinical trial

Pulsed electromagnetic field (PEMF) therapy modulates the immune response and is successfully used in orthopedics to treat osteoarthritis and improve bone regeneration. This may suggest that this treatment may consequently reduce peri-implant soft tissue inflammation and marginal bone loss. To compare clinical, radiographic, and immunological results following nonsurgical treatment for peri-implantitis with or without PEMF therapy. Patients with peri-implantitis were included: pocket probing depth (PPD) between 6 and 8 mm with bleeding on probing (BOP); crestal bone loss between 3 and 5 mm. A novel healing abutment that contained active (test) or inactive (control) PEMF was connected. PEMF was administered via the abutment at exposure ratio of 1/500–1/5000, intensity: 0.05–0.5 mT, frequency: 10–50 kHz for 30 days. Nonsurgical mechanical implant surface debridement was performed. Patients were examined at baseline, 1 and 3 months. Clinical assessment included: plaque index, BOP, PPD, recession, and bone crest level which was radiography measured. Samples of peri-implant crevicular fluid were taken to analyze interleukin-1β (IL-1β). Twenty-three patients (34 implants; 19 control, 15 test) were included. At the follow-up, mean crestal bone loss was lower in the test group at 1 and 3 months (2.48 mm vs. 3.73 mm, p < 0.05 and 2.39 vs. 3.37, p < 0.01). IL-1β levels were also lower in the test group at 2 weeks (72.86 pg/mL vs. 111.7, p < 0.05). Within all the limitation of this preliminary study, the test group improved clinical parameters after a short-term period compared to the control group.     

Immune responses in a mouse model of vitiligo with spontaneous epidermal de‐ and repigmentation

To generate a mouse model of spontaneous epidermal depigmentation, parental h3TA2 mice, expressing both a human‐derived, tyrosinase‐reactive T‐cell receptor on T cells and the matching HLA‐A2 transgene, were crossed to keratin 14‐promoter driven, stem cell factor transgenic (K14‐SCF) mice with intra‐epidermal melanocytes. In resulting Vitesse mice, spontaneous skin depigmentation precedes symmetrical and sharply demarcated patches of graying hair. Whereas the SCF transgene alone dictates a greater retinoic acid receptor‐related orphan receptor gamma (RORγt)⁺ T‐cell compartment, these cells displayed markedly increased IL‐17 expression within Vitesse mice. Similar to patient skin, regulatory T cells were less abundant compared with K14‐SCF mice, with the exception of gradually appearing patches of repigmenting skin. The subtle repigmentation observed likely reflects resilient melanocytes that coexist with skin‐infiltrating, melanocyte‐reactive T cells. Similar repigmenting lesions were found in a different TCR transgenic model of vitiligo developed on an SCF transgenic background, supporting a role for SCF in repigmentation.     

Dual vs. triple therapy for childhood Helicobacter pylori gastritis: a double-blind randomized multicentre trial

BACKGROUND: Data on the efficacy of eradication treatment for Helicobacter pylori gastritis in children are scarce. AIM: To evaluate the efficacy of triple therapy with lansoprazole plus amoxicillin and tinidazole vs. dual therapy with amoxicillin and tinidazole in a double-blind randomized multicentre trial, and the usefulness of eradication in terms of long-term symptom resolution. SUBJECTS: We enrolled 43 consecutive children undergoing endoscopy for upper gastrointestinal dyspepsia with H. pylori gastritis. They underwent a 13C-urea breath test, completed a 2-week symptom diary card, and were randomized. Treatment was given in a Redidose box (Redidose Company Ltd., Brighton, UK) containing either lansoprazole-amoxicillin-tinidazole (triple therapy) or placebo plus amoxicillin-tinidazole (dual therapy) for 1 week. The completion of a 2-week symptom diary card and the performance of a breath test were repeated 6 weeks and 6 months after the end of therapy. One to two years later, a structured telephone interview was conducted with 36 of the children. RESULTS: According to the breath test, 6 weeks after the end of therapy H. pylori was eradicated in 15 of 22 children on triple therapy [68.2%; 95% confidence interval (CI) = 45-88] and in 15 of 21 children on dual therapy (71%; 95% CI = 48-89; not significant), and 6 months after the end of therapy it was eradicated in 16 of 22 children on triple therapy (72.7%) and in 15 of 21 children on dual therapy. Six months after therapy, symptoms were analysed in 11 H. pylori-positive and 31 H. pylori-negative children, and it was found that dyspeptic symptoms had disappeared or improved in both groups, with no difference between them. One to two years later, 36 children were interviewed. Epigastric pain had recurred in three of 26 H. pylori-negative and in seven of 10 H. pylori-positive children (p = .001); in three of the latter, pain was severe and required additional treatment. CONCLUSION: One-week triple or dual therapy with two antibiotics achieved similar eradication rates. Soon after treatment, symptoms disappeared or improved in most children irrespective of eradication, but epigastric pain recurred in the majority of the still-infected children within 2 years.     

Twice-a-day bismuth-containing quadruple therapy for Helicobacter pylori eradication: a randomized trial of 10 and 14 days

Background: Bismuth‐containing quadruple therapy given twice a day for 14 days has been shown to be an excellent first‐line H. pylori eradication therapy. Aim: To compare the efficacy and tolerability of twice‐a‐day bismuth‐containing quadruple H. pylori eradication therapy for 10 versus 14 days in a noninferiority trial. Methods: Dyspeptic patients with H. pylori infection and naïve to H. pylori treatment were randomly assigned to: pantoprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg given b.i.d. (with the midday and evening meals) for 10 or 14 days. Eradication was defined by negative UBT and/or histology 4–6 weeks posttherapy. Efficacy and side effects were determined. Results: A total of 417 patients were randomized (153 men, 264 women; median age 52). Per protocol (PP) treatment success with 14 and 10 days was essentially identical [i.e., 96% (95% CI: 92–98) vs 95% (95% CI: 91–98) for 14 days versus 10 days, respectively. Results with intention‐to‐treat (ITT) analysis were also similar (92% (95% CI, 87–95) vs 92% (95% CI, 88–96)) for 14 and 10 days, respectively. Compliance was excellent in both groups. Side effects were generally mild and similar between groups. Fatigue, discomfort, and vomiting were more common in those in the 14‐day group. The 10‐day regimen costs € 17.65 (ie, approximately 25%) less than the 14‐day regimen. Conclusions: Bismuth‐containing quadruple therapy remained highly effective (i.e., ≥95% PP and >90% ITT) despite reducing the duration from 14 to 10 days.     

A randomized clinical trial of remission induction,consolidation, and chemo-immunotherapy maintenance in adult acute myeloblastic leukemia

Summary The Southeastern Cancer Study Group conducted a randomized clinical trial in acute myeloblastic leukemia and the blastic phase of chronic myelocytic leukemia to compare: Two induction programs (Schedule A) cytosine arabinoside and 6-thioguanine or (Schedule B) cytosine arabinoside, 6-thioguanine and daunorubicin; two consolidation programs (Schedule C) continuation of induction programs at a reduced dose or (Schedule D) a combination of cyclophosphamide, methotrexate and vincristine; and two maintenance programs — (Schedule E) 1 month of BCG, followed by methotrexate or (Schedule F) methotrexate. Over a 3 year period 372 patients were entered and 295 were judged evaluable. None of 11 patients with blastic phase of chronic myelocytic leukemia responded. There were no significant differences between the schedules in the number of patients with acute myeloblastic leukemia achieving complete remissions (37%, Schedule A vs. 41% Schedule B). The relapse rates on consolidation were similar (43%, Schedule C and 39%, Schedule D). BCG significantly prolonged the duration of first remission following consolidation (P<0.05) from 13.0–23.9 weeks. Survival was not significantly prolonged (92.7 weeks vs. 71.7 weeks). There were no serious complications from BCG therapy. Contributors. The following members of the Southeastern Cancer Study Group participated in this study: John T. Carpenter, John R. Durant, Richard Gams, William J. Hammack, George A. Omura, Gayle Roberts, University of Alabama School of Medicine, Birmingham, Alabama; Harold Silberman, Donald S. Miller, Duke University School of Medicine, Durham, North Carolina; William B. Kremer, Durham Veterans Administration Hospital, Durham, North Carolina; Evert A. Bruckner, Lawrence E. Cooper, Charles C. Corley, Joseph E. Hardison, Charles M. Huguley, Jr., James Keller, Mason G. Robertson, John D. Schmale, Charles Vogel, W. R. Vogler, William H. Whaley, E. F. Winton, Emory University School of Medicine, Atlanta, Georgia; Chan Kon Chin, Guy Faguet, Claude-Starr Wright, Medical College of Georgia, Augusta, Georgia; Y. S. Ahn, Howard E. Lessner, University of Miami School of Medicine, Miami, Florida; Dov Gorshein, Scott Murphy, Presbyterian University of Pennsylvania Medical Center, Philadelphia, Pennsylvania; William E. Barry, Sharon P. Fischer, Rosaline R. Joseph, Richard V. Smalley, Temple University School of Medicine, Philadelphia, Pennsylvania; Virgil Loeb, Jr., Cary Presant, Edward Reinhard, Shabbir H. Safdar, Washington University School of Medicine, St. Louis, Missouri; Norman Maldonado, Enrique Velez-Garcia, University of Puerto Rico School of Medicine, San Juan, Puerto Rico; S. A. Gregory, William H. Knospe, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Stephen Krauss, University of Tennessee Memorial Research Center, Knoxville, Tennessee; Karl Tornyos, New Orleans Veterans Hospital, New Orleans, Louisiana; W. B. Forman, R. W. Kellermeyer, A. Rassiga, Case Western Reserve University School of Medicine, Cleveland, Ohio; William R. Arrowsmith, George Porter, Donald M. Samples, Ochsner Clinic, New Orleans, Louisiana; Lois W. Dow, Charles L. Neely, University of Tennessee School of Medicine, Memphis, Tennessee; G. O. Broun, Jr., St. Louis University School of Medicine, St. Louis, Missouri     

Carvacrol improves pulmonary function tests,oxidant/antioxidant parameters and cytokine levels in asthmatic patients: A randomized,double-blind,clinical trial

BackgroundCarvacrol effects on inflammatory mediators, lung pathology and tracheal responsiveness were indicated in animal models of pulmonary diseases.PurposeTo evaluate carvacrol effects on respiratory symptoms, pulmonary function tests (PFT), oxidative stress markers and cytokine levels in asthmatic patients.Study DesignThis study was a randomized, placebo-controlled double-blind, clinical trial.MethodsThirty-three moderate asthmatic patients were divided to the two groups of: placebo group (n = 16) and carvacrol group (1.2 mg/kg/day, n = 17). Prepared capsules were taken for two months along, 3 times/day along with routine medications. Respiratory symptoms, PFT, and oxidative stress markers were evaluated before the treatment (step 0), and one (step I) and two months (step II) after the beginning of the treatment. However, cytokine levels in serum and supernatant of peripheral blood mononuclear cells (PBMC), and their gene expression were evaluated in step 0 and II.ResultsIn carvacrol-treated group, respiratory symptoms significantly decreased after one- and two-month treatment with carvacrol compared to pre-treatment values (p < 0.05 to p < 0.001). Compared to step 0, PFT values were significantly increased in step I and II, in treated group with carvacrol (p < 0.05 to p < 0.001). Most oxidative stress markers were improved following carvacrol treatment (p < 0.05 to p < 0.001). Treatment with carvacrol for two‐month also significantly improved cytokine levels in serum and supernatant of PBMC, compared to step 0 (p < 0.05 to p < 0.001). However, no significant changes were observed in the above-noted parameters in the placebo group.ConclusionDue to anti-inflammatory and antioxidant effect, carvacrol could be suggested as a therapeutic agent for asthma.     

酪酸梭菌活菌散辅助治疗新生儿黄疸的随机多中心临床疗效观察

目的观察酪酸梭菌活菌散(商品名:宝乐安)辅助治疗新生儿黄疸的临床疗效。方法将543例新生儿黄疸患儿随机分为观察组和对照组,观察组274例,对照组269例。观察组在蓝光治疗的同时给予酪酸梭菌活菌散口服,0.5g/次,3次/d,服至黄疸消退;对照组只给予蓝光治疗。于治疗后48h、72h、96h检测血清胆红素值。结果治疗72h、96h后观察组血清胆红素水平较对照组明显下降(P0.05)。结论在蓝光治疗新生儿黄疸的同时服用酪酸梭菌活菌散,可迅速降低胆红素水平,缩短治疗时间。     

Riboflavin as an independent and accurate biomarker for adherence in a randomized double-blind and placebo-controlled clinical trial

Background: Medication adherence is critical for success of clinical trials.

Objective: To assess oral riboflavin is an adherence marker.

Methods: Riboflavin was incorporated into active treatment and placebo pills for a clinical trial lasting for 2 years.

Results: The accuracy (area under the receiver operating curve) of urinary riboflavin was 0.91 as a binary classifier of adherence, and was similar or better than for two active study ingredients daidzein (0.92) and genistein (0.87) (all p?<?0.0001). Decreased adherence over time was similar in the two study groups.

Conclusion: Riboflavin is an accurate and useful biomarker for study pill ingestion.     

Treatment of separation anxiety in dogs with clomipramine: results from a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial

The efficacy and tolerability of clomipramine in the treatment of separation anxiety in dogs was tested in a prospective, randomized, double-blind, placebo-controlled, parallel-group, international multicenter clinical trial. For a diagnosis of separation anxiety, dogs had to exhibit at least one of the following signs in the absence of their owner: destruction, defecation, urination and/or vocalization, as well as the behaviour suggestive of "hyper-attachment" to their owner. A total of 95 dogs were randomized to receive one of the three treatments for 2-3 months: "standard-dose" clomipramine (1 to <2 mg/kg, PO, q. 12 h); "low-dose" clomipramine (0.5 to <1 mg/kg, PO, q. 12 h); and placebo (PO, q. 12 h). All dogs received behavioural therapy. Dogs were examined at four time points (days 0, 28, 56 and 84) after the initiation of therapy. Improvement in each dog's behaviour at days 28, 56 and 84 was evaluated in comparison to its behaviour at day 0.The results showed that, compared to placebo, dogs receiving standard-dose clomipramine were rated improved at least three times faster for the signs destruction, defecation and urination. At most time points, more dogs in the standard-dose clomipramine group were rated improved for the signs destruction, defecation and urination, and in an owner's global assessment of the dog's overall behaviour (p<0.05 at certain time points). However, there were no statistically significant differences at any time point between the standard dose and the placebo groups in the sign vocalization. The low-dose clomipramine group produced no statistically significant effect when compared with placebo. Mild and transient vomiting was noted as a side effect of clomipramine in a small number of dogs.It is concluded that addition of standard-dose (1 to <2 mg/kg, PO, q. 12 h) clomipramine to conventional behavioural therapy for 2-3 months ameliorated the signs of separation anxiety in dogs.     

Efficacy of cranberry juice on Helicobacter pylori infection: a double-blind, randomized placebo-controlled trial

BACKGROUND: Helicobacter pylori infection is a major cause of peptic ulcer disease and gastric cancer. This study postulated that cranberry juice would be effective in the suppression of H. pylori in an endemically infected population at high risk for gastric cancer. MATERIALS AND METHODS: A prospective, randomized, double-blind, placebo-controlled trial was conducted in Linqu County of Shandong Province, China, where 189 adults aged 48.9 +/- 11.2 years (mean +/- SD) with H. pylori infection were randomly divided into two groups: cranberry juice (n = 97) and placebo (n = 92). Participants were assigned to orally receive two 250-ml juice boxes of cranberry juice or matching placebo beverage daily for 90 days. The degree of H. pylori infection was determined using the 13C-urea breath test before randomization at 35 and 90 days of intervention to assess the efficacy of cranberry juice in alleviating infection. RESULTS: A total of 189 subjects with positive 13C-urea breath test results prior to randomization completed the study. At day 35 of intervention, 14 of the 97 (14.43%) from the the cranberry juice treatment group and 5 of the 92 (5.44%) of the placebo recipients had negative 13C-urea breath test results. After 90 days, the study concluded that 14 of the 97 subjects in the cranberry juice treatment group versus 5 of the 92 in the placebo group yielded negative test results. Eleven individuals from the cranberry juice treatment group and only two from the placebo group were negative at 35 and 90 days of experiment. These results are significant (p < .05). CONCLUSIONS: Regular consumption of cranberry juice can suppress H. pylori infection in endemically afflicted populations.     

Effects of Nigella sativa L. seed oil on abnormal semen quality in infertile men: A randomized,double-blind,placebo-controlled clinical trial

In recent years, wide utilization of herbal drugs has encouraged scientists to determine their impressive effects on health. Since Nigella sativa L. seed (N. sativa) has many uses including infertility in traditional medicine, the effects of Nigella sativa L. seed oil on abnormal semen quality in infertile men with abnormal semen quality are of interest. This study was conducted on Iranian infertile men with inclusion criteria of abnormal sperm morphology less than 30% or sperm counts below 20 × 10⁶/ml or type A and B motility less than 25% and 50% respectively. The patients in N. sativa oil group (n = 34) received 2.5 ml N. sativa oil and placebo group (n = 34) received 2.5 ml liquid paraffin two times a day orally for 2 months. At baseline and after 2 months, the sperm count, motility and morphology and semen volume, pH and round cells as primary outcomes were determined in both groups. Results showed that sperm count, motility and morphology and semen volume, pH and round cells were improved significantly in N. sativa oil treated group compared with placebo group after 2 months. It is concluded that daily intake of 5 ml N. sativa oil for two months improves abnormal semen quality in infertile men without any adverse effects.     

Effects of polysaccharide derived from black currant on relieving clinical symptoms of Japanese cedar pollinosis: a randomized double-blind, placebo-controlled trial

We investigated the efficacy of the polysaccharide derived from black currant, named cassis polysaccharide (CAPS), for inhibiting Japanese cedar pollinosis symptoms and improving quality of life by a randomized double-blind, placebo-controlled trial in 2006. A total of 28 subjects were enrolled in the study, and 10 subjects in each group completed the trial. Although there was no significant difference between the CAPS and placebo group in the weekly mean value of any symptom in the daily symptom diary at any time, a smaller degree of final symptom aggravation was found in the CAPS group. Significant aggravation of the score was finally observed in the placebo group with inferior conch swelling and with sneezing, itchy nose, itchy eye and watery eye in the Japan rhino-conjunctivitis quality of life questionnaire assessment, while the changes observed in the CAPS group were not significant. In conclusion, our findings clearly indicate that CAPS would be useful as a food supplement in assisting the treatment of Japanese cedar pollinosis.     

The first transepidermal transplantation of non‐cultured epidermal suspension using a dermarolling system in vitiligo: A sequential histological and clinical study

The current methods for melanocyte delivery to depigmented skin are invasive and often require sophisticated approaches. Here, we describe a promising simple and minimally invasive technique based on the dermarolling system. The technique involves preparation of a keratinocyte/melanocyte suspension prepared by trypsinization from a non‐lesioned part of a patient's scalp skin and transepidermal delivery using a dermaroller equipped with 0.2‐mm needles. Dermarolling leads to epidermal microinjuries without, however, causing pain or inflammation. The technique was applied to facial depigmented areas of five patients with stable vitiligo that were resistant to conventional UV/tacrolimus treatment. The efficacy of cell delivery was analysed histologically on punch biopsies, and repigmentation was evaluated photographically and by clinical assessment. We found that the transplanted keratinocytes rapidly degenerated, leading to keratinization, but melanocytes survived and integrated appropriately into the basal layer of the epidermis, leading to excellent repigmentation after 6 months in three cases and mild repigmentation in two cases. Although based on a small number of patients, we anticipate this technique to become a valid addition to the arsenal of therapeutic approaches to repigmentation in depigmenting disorders.     

Algorithm-based modular psychotherapy vs. cognitive-behavioral therapy for patients with depression,psychiatric comorbidities and early trauma: a proof-of-concept randomized controlled trial

Effect sizes of psychotherapies currently stagnate at a low-to-moderate level. Personalizing psychotherapy by algorithm-based modular procedures promises improved outcomes, greater flexibility, and a better fit between research and practice. However, evidence for the feasibility and efficacy of modular-based psychotherapy, using a personalized treatment algorithm, is lacking. This proof-of-concept randomized controlled trial was conducted in 70 adult outpatients with a primary DSM-5 diagnosis of major depressive disorder, a score higher than 18 on the 24-item Hamilton Rating Scale for Depression (HRSD-24), at least one comorbid psychiatric diagnosis according to the Structured Clinical Interview for DSM-5 (SCID-5), a history of at least “moderate to severe” childhood maltreatment on at least one domain of the Childhood Trauma Questionnaire (CTQ), and exceeding the cut-off value on at least one of three measures of early trauma-related transdiagnostic mechanisms: the Rejection Sensitivity Questionnaire (RSQ), the Interpersonal Reactivity Index (IRI), and the Difficulties in Emotion Regulation Scale-16 (DERS-16). Patients were randomized to 20 sessions of either standard cognitive-behavioral therapy alone (CBT) or CBT plus transdiagnostic modules according to a mechanism-based treatment algorithm (MoBa), over 16 weeks. We aimed to assess the feasibility of MoBa, and to compare MoBa vs. CBT with respect to participants’ and therapists’ overall satisfaction and ratings of therapeutic alliance (using the Working Alliance Inventory - Short Revised, WAI-SR), efficacy, impact on early trauma-related transdiagnostic mechanisms, and safety. The primary outcome for efficacy was the HRSD-24 score at post-treatment. Secondary outcomes included, among others, the rate of response (defined as a reduction of the HRSD-24 score by at least 50% from baseline and a score <16 at post-treatment), the rate of remission (defined as a HRSD-24 score ≤8 at post-treatment), and improvements in early trauma-related mechanisms of social threat response, hyperarousal, and social processes/empathy. We found no difficulties in the selection of the transdiagnostic modules in the individual patients, applying the above-mentioned cut-offs, and in the implementation of MoBa. Both participants and therapists reported higher overall satisfaction and had higher WAI-SR ratings with MoBa than CBT. Both approaches led to major reductions of depressive symptoms at post-treatment, with a non-significant superiority of MoBa over CBT. Patients randomized to MoBa were nearly three times as likely to experience remission at the end of therapy (29.4% vs. 11.4%; odds ratio, OR = 3.2, 95% CI: 0.9-11.6). Among mechanism-based outcomes, MoBa patients showed a significantly higher post-treatment effect on social processes/empathy (p<0.05) compared to CBT patients, who presented an exacerbation on this domain at post-treatment. Substantially less adverse events were reported for MoBa compared to CBT. These results suggest the feasibility and acceptability of an algorithm-based modular psychotherapy complementing CBT in depressed patients with psychiatric comorbidities and early trauma. While initial evidence of efficacy was observed, potential clinical advantages and interindividual heterogeneity in treatment outcomes will have to be investigated in fully powered confirmation trials.     

Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced,metastatic breast cancer: A comparative,randomized, double-blind,placebo-controlled clinical trial

Background: The clinical efficacy of curcumin has not yet been established for the treatment of cancer, despite a large body of evidence from numerous preclinical studies suggesting the therapeutic potential of curcumin, particularly in a synergistic combination with paclitaxel. The main obstacle in using curcumin for adjunctive cancer therapy is its low bioavailability via oral administration.Purpose: We assessed the efficacy and safety of intravenous curcumin infusion in combination with paclitaxel in patients with metastatic and advanced breast cancer.Study Design: A randomized, double-blind, placebo-controlled, parallel-group comparative clinical study was conducted.Methods: A total of 150 women with advanced and metastatic breast cancer were randomly assigned to receive either paclitaxel (80 mg/m²) plus placebo or paclitaxel plus curcumin (CUC-1®, 300 mg solution, once per week) intravenously for 12 weeks with 3 months of follow-up. The primary outcome was determined based on the objective response rate (ORR), as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). The secondary outcomes were progression-free survival (PFS), time to tumor progression (TTP), time to tumor treatment failure (TTTF), safety, and quality of life.Results: The intention-to-treat (ITT) analysis revealed that the ORR of curcumin was significantly higher than that of the placebo (51% vs. 33%, p < 0.01) at 4 weeks of follow-up. The difference between the groups was even greater when only patients who had completed the treatment (61% vs. 38%, odds ratio ==2.64, p < 0.01) were included. A superior effect of curcumin vs placebo was observed in both patients who had completed the treatment and all patients included in the ITT analysis, 3 months after termination of the treatment. No other significant differences were observed between the curcumin and the placebo groups, except for fatigue (3 vs. 10 patients, respectively; odds ratio ==3.7, p = 0.05). However, the patients’ self-assessed overall physical performance was significantly higher with curcumin than the placebo during the treatment and at the end of the follow-up, suggesting better tolerance in the curcumin group.Conclusions: Overall, treatment with curcumin in combination with paclitaxel was superior to the paclitaxel-placebo combination with respect to ORR and physical performance after 12 weeks of treatment. Intravenously administered curcumin caused no major safety issues and no reduction in quality of life, and it may be beneficial in reducing fatigue.Advances in knowledge: This is the first clinical study to explore the efficacy and safety of administering curcumin intravenously in combination with chemotherapy in the treatment of cancer patients.