Impact of Physical Activity and Vitamin D on Osteoarthritic Knee Pain
Condition: Knee Osteoarthritis
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Study type: Interventional

Summary: 
      Knee Osteoarthritis (KOA) is a major cause of pain and disability, particularly in those of
      increasing age and body fat. As there are no very effective therapies for KOA, disease often
      progresses until knee replacement surgery is needed. It has been observed Vitamin D and
      Physical Activity (PA) levels are lower in those with KOA, increased age and body fat. As the
      relationship between KOA, Vitamin D and PA levels are not clearly understood, this study aims
      to explore these relationships and the acceptability/feasibility of PA and Vitamin D
      interventions in those who would likely to benefit from these interventions.

      200-300 people, 50-70 years, BMI 30-40kg/m2, meeting American College of Rheumatology (ACR)
      KOA Guidelines, will be recruited from North Tyneside and Liverpool Hospital trusts November
      2014-January 2016 to participate in a single cross-sectional study visit, which will measure:
      Vitamin D/Calcium serum levels, BMI/Body Fat, mobility, Quality of life and pain (by
      questionnaire), and PA levels.

      Those participants with insufficient Vitamin D levels (25-50nmol/L) and PA levels (<30min
      moderate PA/week), will be invited to take part in a 3 month pilot RCT study.

      >64 people will be recruited for the pilot RCT and equally randomly allocated to 1 of 4
      intervention groups: Vitamin D (1 capsule a day: 2000IU), Placebo (identical capsule: 1 a
      day), PA (online PA programme) and PA and Vitamin D. Additionally at the end of the 12 week
      study visit, up to 20 participants will be invited to take part in a qualitative interview
      exploring their experience during the two studies.
    

Detailed description: 
      The primary aim of this project is to test the feasibility and acceptability of increasing PA
      and Vitamin D supplementation interventions in older, obese people with knee osteoarthritis,
      with low baseline levels of PA and Vitamin D by performing a 2*2 design pilot randomized
      controlled trial and a qualitative interview.

      The secondary aims of this project is to:

        1. Explore the relationships between Vitamin D levels, PA levels and KOA pain (using
           cross-sectional study results)

        2. Estimate effect sizes and inter-individual variation which can be used in the design of
           a future definitive RCT.

      The project refers to 2 integrated studies:

        -  Firstly a cross-sectional study to identify individuals with low vitamin D
           concentrations, low Physical activity levels, who are obese and who meet the ACR KOA
           criteria for knee osteoarthritis.

        -  Secondly a pilot randomized controlled trial, which aims to test the feasibility and
           acceptability of administering vitamin D or placebo capsules and increasing physical
           activity over a 3 month period.

      These 2 studies will run consecutively over 2 winter periods or phases: phase 1 (November
      2014- January 2015: cross sectional study followed by intervention study (February 2015- May
      2015). Phase 2 will run over the same time periods 1 year later.

        1. Cross-sectional study potential participant identification (November 2014-January 2015):

           On Tyneside, the investigators will identify potential participants by screening GP
           surgery patient lists against inclusion criteria (see A17-1). At the Liverpool site,
           participants will be identified by research staff at hospital clinics (obesity).
           Potentially eligible people will be mailed/given a letter of invitation, together with
           information about the study and a consent form to take home and consider. Those
           interested in joining the study will be invited to contact their local research team
           using the contact information provided.

        2. Cross-sectional study screening(November-January 2014/15):

           Potential participants will complete a brief telephone screening questionnaire when they
           call to register their interest in the study to verify their eligibility. The CI will
           then call back to inform the potential participant of their eligibility and, if
           eligible, an appointment will be made to attend for the cross-sectional study visit
           (study visit 1).

        3. Cross-sectional study visit: study visit 1 (November-January 2014/15):

           Participants will attend an appointment at North Tyneside General Hospital or Aintree
           Hospital Liverpool (depending on their research site) lasting 1 hour 30 minutes. The
           visit will begin by reviewing the participant information sheet and completing the
           consent form. After this, several measurements will be completed:

             -  Blood samples

             -  Questionnaires

             -  Body composition At the end of the study visit, the participants will be given a
                accelerometer to wear for the next 3 days. Participants will be provided with
                instructions on accelerometer use, activity log and a prepaid envelope in which to
                return the device.

        4. Screening for eligibility for pilot RCT (January 2015):

           Using data from the cross-sectional study, participants with low vitamin D concentration
           (25-50nmol/L) and low physical activity levels (<30min/week moderate activity)will be
           invited to participate in the pilot RCT.

        5. Pilot RCT starter session (study visit 2) (February 2015/16):

           Participants will attend a starter session for the pilot RCT study at North Tyneside
           General Hospital or Aintree hospital Liverpool. Prior to their appointment, all
           participants will be randomly allocated (stratified by gender) to 1 of 4 treatment arms:

             -  Vitamin D supplementation: 2000IU/day vitamin D capsule

             -  Placebo: 1/day edible oil capsule (identical to vitamin D capsule)

             -  Physical activity intervention (online system to record daily step using a
                pedometer provided, which slowly increase step and physical activity goals)

             -  Vitamin D + Physical activity intervention.

           The investigator will explain how to undertake the intervention, provide study materials
           and answer any questions the participant may have. Vitamin D and Placebo intervention
           will be blinded to the participants.

        6. 6 week follow up (study visit 3)(March 2015/16: All pilot RCT participants will be
           invited back at 6 weeks into their intervention period for a study visit lasting 1-1hr
           15 minutes, at either NTGH or UHA. The same measurements taken during the
           cross-sectional study visit will be taken with some additional compliance measures.

        7. 12 week follow up (study visit 4) (April/May 2015/16): All pilot RCT participants will
           be invited back at 12 weeks into their intervention period for a study visit lasting
           1-1hr 15 minutes at NTGH or UHA. This will be the study close for those not taking part
           in the qualitative interview. The same measurements will be taken as in study visit 3.
           Participants will be mailed feedback on their study measures including vitamin D status.

        8. Qualitative interview (April/May 2015/16):

      A subset of up to 20 participants will be invited to take part in a qualitative interview at
      NTGH or UHA directly after study visit 4. The interview will last 1hr and explore
      participants views in a range of topics which may identify areas of improvement in the
      design, delivery or practical arrangements of the studies in order to inform future studies
      in this area.
    

Intervention name(s): Vitamin D3 2000IU/daily 3 months; PA intervention People with Osteoarthritis Walking Programme; Placebo capsule (Vitamin D): edible oil
Intervention type(s): Dietary Supplement; Behavioral; Other
Intervention description(s): Vitamin D will be provided in the form of a daily capsule over 3 months containing 2000IU of Vitamin D3 suspended in oil (manufactured and provided by DSM) with the aim of raising 25OHD levels to sufficiency (>50nmol/L) by 3 months.; The PA intervention will aim to increase levels of PA safely in our defined population. Participant are given a pedometer at the start of the intervention and encouraged to record their daily step counts and set step goals using the online system provided (POW: People with osteoarthritis walking programme).; Placebo capsules will be administered over 3 months, as daily capsules (identical to Vitamin D capsules) containing edible oil (manufactured and provided by DSM)
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Knee osteoarthritis; Pain; Vitamin D; Physical activity; Pilot study; Qualitative Interview; Obesity; Older adults