The Effect of n-3 Polyunsaturated Fatty Acids in Patients With Psoriatic Arthritis
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|ClinicalTrials.gov Identifier: NCT01818804|
Recruitment Status : Completed
First Posted : March 27, 2013
Last Update Posted : February 18, 2016
|First Submitted Date ICMJE||March 20, 2013|
|First Posted Date ICMJE||March 27, 2013|
|Last Update Posted Date||February 18, 2016|
|Study Start Date ICMJE||March 2013|
|Actual Primary Completion Date||December 2015 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Change in HRV measure [ Time Frame: Baseline and 24 week ]
Heart Rate Velocity, non-invasive measurement for the autonom regulation of the heart associated with risk of cardiovascular disease
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01818804 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Change in PWV [ Time Frame: Baseline and 24 weeks ]
Pulse wave Velocity, non-invasive measurement for arterioscleroses
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE
||Change in Inflammation parameters [ Time Frame: Baseline and 24 weeks ]
Disease activity score for psoriatic arthritis, Psoriasis area severity index, enthesitis score, CRP
|Original Other Outcome Measures ICMJE||Same as current|
|Brief Title ICMJE||The Effect of n-3 Polyunsaturated Fatty Acids in Patients With Psoriatic Arthritis|
|Official Title ICMJE||The Effect of n-3 Polyunsaturated Fatty Acids on Risk Markers for Cardiovascular Disease and Inflammation in Patients With Psoriatic Arthritis|
Background: There is evidence for a high cardiovascular risk in rheumatic and inflammatory diseases . Recent evidence suggest that psoriatic arthritis is also associated with an increased cardiovascular risk with accelerated atherosclerosis and increased cardiovascular risk. However, data regarding cardiovascular comorbidity and cardiovascular risk factors in patients with psoriatic arthritis are limited.
Objective: The aim of this study is to investigate the effect of daily supplementation with 3 g n-3 polyunsaturated fatty acids on risk markers for cardiovascular disease and inflammation in patients with psoriatic arthritis.
Design: Randomized double-blind, placebo-controlled, multicenter trial with n-3 polyunsaturated fatty acids in patient with psoriatic arthritis.
Setting: Departments of Rheumatology, Nephrology and Cardiology at Aalborg University Hospital and Vendsyssel Hospital in Region Northern Denmark
Participants: 156 men and women aged > 18 years with psoriatic arthritis classified by the CASPAR criteria will be included. Exclusion criteria: cardiac arrhythmias, conduction disturbances, treatment with biological drugs or oral corticosteroids. Inclusion time: spring 2013 to spring 2015.
Method: The following data will be collected for each participant: Interview including dietary records, assessment of tender and swollen joints, enthesitis, dactylitis, patient global assessment of disease activity (Visual Analogue Scale ), global assessment of pain (Visual Analogue Scale), psoriatic skin involvement by Psoriatic Area and Severity Index (PASI), laboratory parameters of disease activity and risk markers of cardiovascular disease.
For detection of early cardiovascular risk markers Heart Rate Variability (HRV) and Pulse Wave Velocity (PWV) will be performed.
Main outcome measures: The primary endpoint will be HRV and secondary endpoints will be PWV, inflammatory activity and use of analgesics.
The trial is approved by The local Ethics Committee, registration number N20120076
Method Study design: The study was designed as a randomized, double-blind, placebo-controlled, multicenter trial. The patients were randomly assigned in blocks of five by a computer-generated block sequence. For 24 weeks patients were assigned to daily intake of 6 capsules containing either 3 g of n-3 PUFA (50% EPA and 50% DHA) from fish oil capsules or 3 g of olive oil (approximately 80% of oleic acid and 20% linoleic acid). All the investigators, patients and research staff were blinded to the supplementation codes. Patients were asked to maintain their usual diet during the whole study. The study was conducted in accordance with the Declaration of Helsinki and Good clinical practice (GCP).
Subjects: Patients with PsA defined by Classification criteria for psoriatic arthritis (CASPAR) (25) were enrolled from the Departments of Rheumatology, Aalborg University Hospital and Department of Rheumatology, Vendsyssel Hospital, in Denmark. The inclusion criteria were PsA in adult above 18 years of age with any disease activity while exclusion criteria were documented cardiac arrhythmias, treatment with biological drugs or treatment with oral corticosteroids.
Compliance was assessed by counting capsules during the last visit. Patients were defined as non-compliant if >150 capsules were returned and those were not included in the per-protocol analysis.
All participants gave their written informed consent and the regional ethics committee of Northern Region Denmark, approved the study.
Clinical assessment: Patients were assessed at baseline, after 12 weeks of supplement and after 24 weeks. At baseline, duration of disease, medical history, smoking habits and diet were obtained Medical history of diabetes mellitus, hypertension and dyslipidemia were assessed and was defined as present if the patient received dietary or medical therapy for the condition. A food questionnaire was used to assess patients' fish consumption at lunch and dinner. A score for fish intake was given according to the following: never eat fish = 1; eat fish once a month =2; eat fish two to three times a month = 3; eat fish once a week = 4; eat fish two to three times a week = 5; and eat fish at least once daily = 6.
At each visit conventional cardiovascular risk factors such as smoking habits, blood pressure, body mass index (BMI) and waist to hip ratio (WHR) were assessed in all patients. Additionally, a clinical evaluation was performed, consisting of 68 tender joint count, 66 swollen joint count, disease activity score (DAS) and psoriatic skin area involvement (PASI).
Blood samples: Blood samples were taken non-fasting in the morning for assessment of fatty acid composition of granulocytes and routine laboratory evaluation. Granulocytes were isolated from whole blood, and lipids were extracted and fatty acids esterified as previously reported (26). The fatty acid composition in granulocytes were determined by gas chromatography with a Chrompack CP-9002 gas chromatograph (Varian, Middelberg, The Netherlands) and expressed as weight percent (wt. %) of total fatty acids.
HRV: Five min HRV recordings were obtained with SphygmoCor Technology (SphygmoCor, Software version 8.2; AtCor Medical, Sydney, NSW, Australia).
HRV was recorded in each patient according to current recommendations (27). The measurements were obtained in the morning hours after resting for 15 min in a room with a constant temperature of 20°C. Patients were instructed not to smoke and avoid alcohol and caffeine-containing beverages within 12 h prior to investigation. A trained technician blinded to the type of supplement performed these analyses. The patients were placed in a supine position (resting) for 10 min, breathing spontaneously without talking. HRV were analysed in the time-domain and the following variables were used:
PWV: PWV and pulse wave analysis were performed non-invasively with the Sphygmocor system (AtCor Medical, Sydney, NSW, Australia), as described previously (28) and according to international recommendations (29). All measurements were made in duplicate by a single trained operator and the mean of the two values was used in the analysis.
Carotid-radial and carotid-femoral PVW was measured using arterial tonometry. All measurements were performed on the right side extremities. The surface distance was measured with a tape measure as a straight line from the suprasternal notch to the carotid location (proximal pulse) and subtracted the distance from the suprasternal notch to the radial or femoral location (distal pulse) (30,31). The pressure wave transit time was determined as the time between the R-wave of the ECG and the proximal pulse subtracted from the time between the R-wave of the ECG and the distal pulse. PWV was subsequently calculated by dividing the surface distance by the pressure wave transit time.
The central BP was estimated using the SphygmoCor® device. After 10 min of rest in the supine position, brachial BP was measured three times at 2-min intervals on the left arm with the automatic Microlife® device, and the last measurement was taken as representative of brachial artery BP. Hereafter, radial artery pressure waveforms of the right arm were sampled. Using the validated generalized transfer function, central BP was estimated using brachial systolic and diastolic BP (32,33). Aortic augmentation index (AIx) was standardized to a heart rate of 75 beat per minute to minimize the effect of the heart rate. Only measurements with T1 (the time to the initial upstroke of the pressure wave) >80 and <150 ms and augmentation index (AI, the difference between the first and second peak of the arterial waveform as percentage of the pulse pressure) <50% and operator index (an arbitrary number between 1 and 100 describing the quality of the derived pulse wave) >80 were accepted according to recommendations (AtCor Medical® website).
Statistical Analysis All statistical analyses were performed using STATA version13 (StataCorp LP, TX, US) We hypothesized that intervention with n-3 PUFA would increase the HRV parameter RR by 0.5 of a standard deviation (SD).
To achieve this at p<0.05 and 1-β = 0.80 we needed a sample size with 63 subjects in each group.
The difference in the continuous outcomes between baseline and 24 weeks after randomization was compared between the two treatment groups in a one-sided analysis of variance (ANOVA). Equality of variances between the treatment groups was assessed using Bartlett's test. Due to the potential for confounding after the random treatment assignment an analysis of covariance (ANCOVA) was performed. Prior to this analysis a check for collinearity between the covariates was performed and the model was modified accordingly. In this model equality of variances was assessed using Levene's test.
The total number of parameters in the models was restricted to one tenth of the number of study participants or number of each category when specifying the models.
All analyses were performed both as intention to treat (none of the patients are excluded and the patients are analyzed according to the randomization scheme) and per-protocol (patients who complete the entire clinical trial according to the protocol) analyses. The analyses were controlled for age, sex, smoking status, presence and absence of diabetes mellitus, hypertension and hypercholesterolemia, the use of nonsteroidal anti-inflammatory drugs (NSAID) and disease activity scores.
Differences were considered significant with a p-value of <0.05 (two-tailed).
|Study Type ICMJE||Interventional|
|Study Phase||Not Applicable|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Condition ICMJE||Psoriatic Arthritis|
|Publications *||Kristensen S, Schmidt EB, Schlemmer A, Rasmussen C, Lindgreen E, Johansen MB, Christensen JH. The effect of marine n-3 polyunsaturated fatty acids on cardiac autonomic and hemodynamic function in patients with psoriatic arthritis: a randomised, double-blind, placebo-controlled trial. Lipids Health Dis. 2016 Dec 12;15(1):216.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date||December 2015|
|Actual Primary Completion Date||December 2015 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 80 Years (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Denmark|
|Removed Location Countries|
|NCT Number ICMJE||NCT01818804|
|Other Study ID Numbers ICMJE||N-20120076|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||
|Responsible Party||Salome Kristensen, Aalborg Universitetshospital|
|Study Sponsor ICMJE||Aalborg Universitetshospital|
|Collaborators ICMJE||Not Provided|
|PRS Account||Aalborg Universitetshospital|
|Verification Date||February 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP