CTRI Number	CTRI/2022/03/040726 [Registered on: 02/03/2022] Trial Registered Retrospectively
Last Modified On:	25/02/2022
Post Graduate Thesis	Yes
Type of Trial	Interventional
Type of Study	Nutraceutical
Study Design	Other
Public Title of Study Modification(s)	The effect of potassium rich diet in Rheumatoid arthritis
Scientific Title of Study	The effect of potassium augmentation on pain in patients of RA under supervised standard of care treatment
Secondary IDs if Any	Secondary ID  Registry  NIL  NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)	Name  TOKTAM KIANIFARD  Address  Center for Rheumatic Diseases(CRD), Hermes Elegance, 1988 Convent street, Camp,Pune Pune MAHARASHTRA 411001 India  Phone  07507083222   Fax     Email  toktam_kiani81@yahoo.com
Details Contact Person Scientific Query Modification(s)	Name  ARVIND CHOPRA  Address  No11.Hermes Elegance 1988,Convent Street,Camp. Pune Pune MAHARASHTRA 411001 India  Phone  02026344099   Fax  91-20-26350084   Email  crdp@vsnl.net
Details Contact Person Public Query Modification(s)	Name  ARVIND CHOPRA  Address  No11.Hermes Elegance 1988,Convent Street,Camp. Pune Pune MAHARASHTRA 411001 India  Phone  02026344099   Fax  91-20-26350084   Email  crdp@vsnl.net
Source of Monetary or Material Support	Arthritis Reseach and Care Foundation-Center for Rheumatic Diseases(CRD),Pune
Primary Sponsor	Name  Dr ARVIND CHOPRA  Address  Center for Rheumatic Diseases, hermes Elegance, 1988, Convent street, Camp, Pune  Type of Sponsor  Other [Research institution and private clinic]
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	India
Sites of Study Modification(s)	No of Sites = 1   Contact Person  Name of Site  Site Address  Phone/Fax/Email  TOKTAM KIANIFARD  Center for Rheumatic Diseases  Rheumatology Department, 11, Hermes Elegance,1988,convent street,Camp. Pune   7028913929 toktam_kiani81@yahoo.com
Details of Ethics Committee Modification(s)	No of Ethics Committees= 1   Name of Committee  Approval Status  CRD Ethic Committee  Approved
Regulatory Clearance Status from DCGI	Status  Not Applicable
Health Condition / Problems Studied	Health Type  Condition  Patients  RHEUMATOID ARTHRITIS
Intervention / Comparator Agent	Type  Name  Details  Comparator Agent  Active control arm  The active control arm is routine diet being consumed by the patient . No dietary advice is given to this group. Patients will continue the standard rheumatology care.  Intervention  Arm 1  Active intervention arm 1- K+ rich diet using natural source. This increases the daily oral K+ intake by 3.5-4.1 gm. In this arm, the dietary sources advised are in categories and each categories contains 2-3 recommendations of diet items ; cereal, pulses, fruits and vegetables are the categories and diet items are Ragi, Wheat, Bajra, Jowar, Tur dal,Mong dal, Chawli, Shevga vegetable, Brinjal,Karela, Banana,Musambi. patients will continue standard Rheumatology care.  Intervention  Arm 2  Active intervention arm 2- this contains the K+ rich diet described in arm 1 and a K+ supplement. This supplement is made up of powder dietary items in standardized proportions mixed with standard oral rehydration salt (sold in the market as ORS to correct dehydration containing sodium chloride, potassium chloride, bicarbonate and glucose as per recommendation of Indian pharmacopeia and sold as over the counter.) The dietary items in the supplement are Chawli, moon dal, coriander seed and jeera seed. This diet based supplement will provide 4.1gm oral potassium daily in addition to the K+ rich diet . The patients will continue the standard rheumatology care
Inclusion Criteria Modification(s)	Age From  18.00 Year(s) Age To  75.00 Year(s) Gender  Both  Details  1. Patients diagnosed RA according to American College of Rheumatology 1987 classification criteria and the new ACR/EULAR 2010 criteria 2.RA disease duration ≥6 months 3.Pain VAS ≥ 4 cm (10 cm scale) 4.Requiring frequent pain relieving medication for over 2 weeks or moderately severe pain interfering with daily activities of at least 2 weeks duration 5.Patient receiving supervised standard of care treatment for RA for at least 12 weeks. 6.Able to understand the study and willing to give written informed consent
ExclusionCriteria	Details  1.Oral steroid equivalent prednisolone >10 mg daily and unstable consumption of 4 weeks prior to screening. 2.Male or female patients <18 years of age or >75 years of age 3.Patients with abnormal kidney function test as per standard laboratory criteria. 4.Serum K+ level˃5.5 mEq/L 5.Patients with Uncontrolled diabetes and hypertension 6.Patients on diuretics or any drug altering serum K+ 7.Pregnant or breast feeding women 8.Patients who are incapacitated largely or wholly bedridden. 9.Patients on any herbal, homeopathic or ayurvedic medicine. 10Patients with history of heart failure or unstable angina. 11. History or presence of any medical or psychiatric condition. 12.Any other concern as per discretion of rheumatologist
Method of Generating Random Sequence	Computer generated randomization
Method of Concealment	An Open list of random numbers
Blinding/Masking	Investigator Blinded
Primary Outcome	Outcome  TimePoints  Reduction in maximum pain experienced during last 24 hours measured on Visual Analogue Scale  Baseline and follow up end points at monthly interval up to study completion at 16 weeks (0,1 month, 2 months, 3 months and completion)
Secondary Outcome	Outcome  TimePoints  Joint Counts for pain/ swelling, Physician and patients global assessment, Health assessment questionnaire RA pain score, SF36(Physical and mental), ESR,CRP titer,DAS 28 (Disease Activity Score/EULAR), ACR index improvement(@0%,50%,70%)   Baseline and follow up end points at monthly interval up to study completion at 16 weeks (0,1 month, 2 months, 3 months and completion)
Target Sample Size	Total Sample Size="172" Sample Size from India="172"
Phase of Trial	N/A
Date of First Enrollment (India)	12/02/2014
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="0" Months="4" Days="20"
Recruitment Status of Trial (Global) Modification(s)	Not Applicable
Recruitment Status of Trial (India)	Completed
Publication Details	Not yet submitted
Brief Summary Modification(s)	The aim of the study is to investigate the role of  potassium (K+) in reducing pain in patients suffering from rheumatoid arthritis.  The oral intake of  K+ will be increased  by using known dietary sources  rich in K+ and easily available K+ supplement. Suitable consenting patients on supervised standard rheumatology care in community based referral clinic  (CRD, Pune) will be randomized into one of the three arms- augmented dietary K+, augmented dietary  K+ using dietary sources and K+ supplement and routine diet (active control). This will be a randomized single blind (investigator) parallel efficacy three arm active control study of 16 weeks duration carried out in a single center. The study sample sized was calculated based on the primary efficacy of  reduction in  pain on visual analogue scale with 80% power (Type II error) and significant p < 0.05 (Type I error). Secondary efficacy measures include reduction in clinical and laboratory measure of disease activity and improved functional and quality of life indices. Patients will be monitored for any adverse event and expected K+ related side effects. Patients will be monitored at four weekly intervals till study completion. Patients will be examined by rheumatologists and other trained study personnel. The protocol was approved by the ethics committee (CRD, Pune) and will adhere to guidelines on clinical trials issued by ICMR, GCP and ICH/WHO. The intervention by K+ rich diet and by K+ rich supplement will increase the daily oral K+ intake by 3.5-4.1 gm and 4.1 gm respectively. Patients randomized to intervention arms will be provide with personal discussion and special brochures in local language. 171 patients of RA have been enrolled in the study.   The dietary survey in the pilot study showed that  dietary K+ was low (p<0.5) in RA patients and more so in women (p<0.05). It further showed that the rest of the RA diet was well matched with Indian standards of RDA and seemed adequate in proteins, fats, minerals and vitamins. The Indian version of RAPS was determined to have face and content validity with a fair-good correlation with several measures of disease activity and quality of life; used in main study. Pain and efficacy measures improved (P<0.05) by intervention; difference was NS by intent to treat analysis (mean change pain VAS: A=-1.3 cm; B=2 cm; C= 1.2; p=0.17, ANOVA).But completer analysis showed significant change (p=0.04)in mean pain VAS in Arm  B(K+ supplement).B arm showed best response (P<0.05) in proportion patients with at least 50% reduction and minimal clinical important difference in pain VAS on completion from baseline. B arm also showed maximum improvement (NS) in HAQ (Indian validated version) and SF 36 physical score. There was reduction (NS) in in mean DAS 28score (A:-1.4;B:-1.2;C:-0.9). Only mild adverse events were reported (<8% patients by study arm). Routine laboratory measures of hemogram, metabolic renal hepatic parameters remained normal. None withdrew due to AE. Withdrawal rate was ~10% and mostly due to logistic issues. On completion, B arm demonstrated a maximum serum cortisol (AM) increase. K+ intervention arms showed reduction in systolic BP. Ongoing medication, dietary factors and compliance, disease activity status may confound results. The inverse association (r=-0.22) between dietary K+ and pain VAS was significant (p<0.01), albeit modest. Disease  duration, serum K+, allocation to Diet K+ arm and body mass index were significant predictors of  pain relief (pain VAS) in a robust logistic regression model. Conclusion: The diet of RA patients is insufficient in K+  though of adequate match to Indian standards. An Indian version of RAPS was found valid for measuring pain. This pragmatic study showed a clinically important pain reduction, though modest, over and above that obtained by standard care using  dietary K+ augmentation. Other possible benefits were reduced disease activity and improved BP (cardiovascular) status. Overall, this seemed to be a gentle useful adjunct therapy in RA.