A randomised control trial of diet in adults

A randomised control trial of diet in adults with previously untreated PKU Lesley Robertson Research Dietitian The National Hospital for Neurology and Neurosurgery University College London Hospitals

PKU Learning Disability Research Group n n n Formed 1999 Designed the protocol and secured funding for the study Members of the Steering Group : Dr Philip Lee Professor Glynis Murphy Dr Brian Fitzgerald Eleanor Weetch Rosemary Hoskin Maggie Lilburn Pat Portnoi Carole Coleman

Outline of presentation n n n n Katie’s story Finding participants Background and summary to the project Outcome of the 36 participants Blood results Behaviour results Summary Story of Janet, a lady who participated in the trial

What we have discovered ? n n n Statistics led us to believe there could be 1500 – 1800 people living in the UK with untreated PKU To date, we have found 157 adults – living predominately in care homes for people with learning disability We recruited 36 people onto the trial

Barriers to locating and recruiting n n People’s medical notes don’t follow them around – staff unaware of diagnosis Staff – social care and local medical teams suspicious of research n n n Either to give initial info when locating Consent to be part of trial Care staff unable to accept PKU diet, feel cruel, “I couldn’t cut out meat, why should they”

Charactersitics of 157 adults identified

Social care needs of adults suitable for the trial

Medical Symptoms

Wellcome Trust Grant n n Funded 3 year study – to assess the effect of low phenylalanine diet in 36 previously untreated adults Two full time researchers : psychologist and dietitian Researchers started on the project in Summer 2003 Support from n n n NSPKU SHS Steering Group

National study Hull Manchester Sheffield Lancaster London Walsall Cheltenham Somerset South Wales Bristol Birmingham Dudley Hertfordshire East Sussex Norfolk Berkshire Kent Hereford&Worcester

Inclusion Criteria n Adults with PKU but never treated by diet n Severe learning disability n Presence of challenging behaviour n Plasma phenylalanine > 1200 µmol/L n Consent from carer and or family

Research Protocol n n n A double-blind placebo crossover trial to assess the efficacy of phenylalanine restriction in 36 adults previously untreated PKU Length of trial - 60 weeks split into 4 sections – including a trial of a PKU and a non-PKU diet Behaviour monitored throughout each phase

Research Protocol Diagram Baseline (8 weeks) Diet One (24 weeks) Non PKU diet Visit 1 Visit 2 Non PKU diet Wash-out PKU Diet Two (24 weeks) PKU Diet Visit 3 Visit 4 Visit 5

Dietary Management n n n Normal care home diet eaten during the baseline and washout Food in diet 1 and 2 was low phenylalanine Amino acid supplement - the difference in two phases On active diet (PKU diet) XP Maxamum given On placebo diet (non PKU diet) the amino acid supplement contained phenylalanine – P Maxamum

Monitoring – blood and behaviour n n Blood tests – weekly finger pricks Behaviour monitoring n n n Daily behaviour diary 2 standardised questionnaires at each of five visits 3 short video’s of each participant at the five visits

The 36 Adults enrolled onto the trial n 17 completed full 60 weeks n n 3 withdrew on diet 2(following deterioration of behaviour) to follow PKU diet 7 withdrew during baseline n n n 9 remain on PKU diet 8 on returned to normal diet 4 unable to do bloods 3 disliked amino acid supplement 5 withdrew during diet 1 – all unable to take amino acid supplement 3 withdrew at carers request on diet 2 1 withdrawn as failed to meet study criteria

Blood Phenylalanine

Behaviour Monitoring n Daily behaviour diary n n Standardised questionnaires n n n 3 positive behaviours 3 negative behaviours Carers comments Vineland Adaptive Behaviour Scales (VABS) Aberrant Behaviour Checklist (ABC) Video of 3 situations n n At mealtime, doing puzzles, on own Measured time spent (in seconds) on challenging behaviour, concentration on task, and communication

Daily Behaviour Diaries n 3 positive behaviours - standardised for everyone n n 3 Negative behaviours- individualised n n n n Concentration Social responsiveness Communication Screaming, shouting Aggression - grabbing, hitting, punching Invading space Self harm Smearing and/or stripping Agitation Hitting/banging doors or throwing things Carers comments

Behaviour Analysis – daily diary n Daily behaviour diary n No correlation n n between Phe level and negative behaviours No correlation between Phe level and positive behaviours No correlation between negative behaviours and positive behaviours Very positive carer comments - 250 were analysed and statistically significant – 0. 001

Carers comments n We have some clear descriptions of clients’ changed behaviour n n n Intensity of negative behaviour decreases Length of negative behaviour deceases Receptive to others and aware of others feelings – allowing staff to work on improving negative behaviour Communication becomes clearer and more concise The participants often been undertaking behaviour for many years – time is needed to see marked benefit and undo learned behaviour

Carer comment She’s more willing to try new things, and we can interact more with her. If she doesn’t like it, she doesn’t dig her fingernails in – just holds her hand away. Stays in the bath – very chilled, no screaming: before, staff had to stay in bathroom with her. Will spend time in kitchen watching what you are doing. When out in the community, used to need a wheelchair – now she walks. In June, we had to wait in hospital to see the consultant and she waited quietly for quite a long time. Neurologist wired her up and she was OK – before she would not let doctors near her.

Carer comment He went round supermarket with a shopping basket. Took great pains to choose shampoo – same colour as his bedroom. New activity – colouring/scribbling, folding laundry: towels folded and put away (if shown where). Fully involved in bedmaking, rather than just watching. If prompted, will clear away other people’s plates. More patience with game playing – quoits especially – will take turns. Uses tissue to blow own nose. Involved with others, participates. Allows another resident to hold his hand. Shares sweets. Goes on van trips now with others. Into pubs. If he wanted a drink, before would take you to cup, now also teabag, open cupboard, pointing to supplement.

Carer comment One day last week, she took her pills out of her day-centre bag – unzipped it! – and put them on the window sill in the kitchen (not done before). Last night carer was really tired and wanted to go to bed, but she remade the bed and put the light on (i. e. stopped her from going to bed). Last weekend she didn’t want to be outside (in covered area by front door) and took carer by hand led her back indoors/upstairs. Took her coat off by herself. She is calmer, to extent that they don’t need 2 staff members with her always now (though still 2 at meals). Mimicked carer (stroking hair). Fun/playful. Relaxed, eye contact. Put extra cup out for staff’s coffee.

Carer comment More independent – will ask for something he wants. We were going to visit his mum – he put on his own shoes, got his coat and stood by the ‘going out’ door. Will go in the garden on his own, going through 2 doors. Will take staff’s hand to go down to the bathroom/bedroom. In last 3 weeks, has taken off his pad for 3 -4 hours, will sit in kitchen, gets up and goes to toilet – bowels and wee – independently or asks staff. Moves around of own volition, in control – not needing prompting from staff as before. He decides where he goes and doesn’t stay put (as before) – moves between bathroom, kitchen, dining room, his room and outside. If he wants curtains closed, he does it or he asks staff (moves your hand towards curtains – very clear. To go out, got shoes, pulled me to wardrobe). Seems to understand what options are, that can do when he wants and what consequences are.

Standardised Questionnaires n No significant difference between active and placebo on either n n Vineland Adaptive Behaviour Scales (VABS) Aberrant Behaviour Checklist (ABC) Need a more sensitive tool Katie’s story

Video data collected at visits n No differences between phases – i. e. between Normal diet, Active diet or Placebo diet: n n Observed instances of challenging behaviour Time concentrating during meal or on task Observed gestures, repetitive speech and conversation Interest and success doing puzzles

Summary n n n Difficult to find adults with previously untreated PKU 36 people recruited to the trial Blood results of 17 completers n n n BL 1582 µmol/L PKU diet 572 µmol/L WO 1520 µmol/L Non PKU diet 1474µmol/L Carers comments most powerful evidence when analysing behaviour From the 17 completers and the 3 who withdrew early to follow PKU diet, 60% are still on diet

Thank You n n n To Jan and Carolyne Care Homes Steering Group NSPKU SHS My colleagues at Charles Dent Metabolic Unit, The National Hospital for Neurology and Neurosurgery, University College London Hospitals