Clinical trial NCT04611074: Health-related Quality of Life in Patients at Nordic Clinic
Official title: Health-related Quality of Life and Symptom Burden in Patients at Nordic Clinic Before, During and After Personalised, Functional Medicine Treatments and Lifestyle Interventions
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Chronic Disease
Keywords: Chronic Disease
Lead sponsor: Nordic Clinic Stockholm
Sponsor class: OTHER
Collaborators: name: Stockholm University
First posted: 2020-11-02
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All Swedish speaking patients (\>1= 18 years) visiting the clinic will be asked to participate in the study by clinic personnel when they are visiting the clinic. All patients at the clinic are able to provide informed consent and to fill out online forms.

Brief summary: Nordic Clinic is a private clinic for personalised treatment based on the Functional Medicine concept. In summary, functional medicine is aimed at addressing the lifestyle and behavioral factors that are believed to contribute to the symptoms the patient suffers from. In short, the treatment is based on a timeline of health-related life events, current lifestyle factors and behaviors and physiological examinations to develop a personalised lifestyle program. The main component of the treatment provided at Nordic Clinic is in-depth lifestyle coaching to achieve the desired behavioral and lifestyle changes.

Working at the clinic is a clinical physiologist, nutritionist, physician specialist in general medicine and researchers work. The vast majority of people who apply for the clinic have long-standing symptoms that have been investigated by the healthcare system without any organic explanation for the symptoms having been identified. Common causes are gastrointestinal problems, persistent fatigue and insomnia. The aim of the study is to investigate symptom-borne and health-related quality of life during and after treatment and to identify predictors of improvement of health-related quality of life. The main purpose is to investigate whether the health-related quality of life is improved during treatment. This is an observational study and all adult patients who are able to complete the web form in Swedish at the clinic are asked to participate. Participants who give consent will receive a link to the questionnaire via email once a month for one year and once after two years. Participants are recruited for two years, and will be completed after the last questionnaire is completed by the last included participant, ie autumn 2022. In addition to the self-assessments, the number of visits to the clinic, sampling and results, who finances the treatment and treatment plan are recorded.

The first aim is to investigate improvement in symptom burden and health related quality of life during and after treatment (does symptom burden and health related quality of improve during treatment and are improvements stable at the 2 year follow-up?) The second aim is to investigate factors that predict recovery (Do persons with a high level of motivation for behavioural change experience a better improvement in symptom burden and health related quality of life than persons with a low level of motivation for behavioural change?).

Detailed description: Research plan

Health related quality of life in patients at the Nordic Clinic

Background

Nordic Clinic is a private clinic that provides personalised treatment based on functional medicine. The vast majority of the patients seeking care at the clinic suffer from unexplained medical symptoms, most commonly fatigue and abdominal symptoms, and have previously been medically evaluated by health care. Working at the clinic are a clinical physiologist, nutritional therapist, licensed physician and a researcher. Patients follow a clinical treatment process starting with the physician progressing through to the nutritionist. Treatment is covered either by the patient themselves, by employers or health insurances.

Before treatment is initialised, an extensive medical history along with current lifestyle habits are taken. The treatment programme is based on lifestyle factors, mainly diet, sleep, stress management and physical activity. Supplements are given. Drugs are prescribed sparsely and by a licenced physician, and may include Rifaximin or other antibiotics for intestinal bacterial overgrowth, motility drugs for constipation, anti-parasitic drugs in case of parasite infection, and melatonin for sleep disturbances.

The components in the treatment programme have been investigated separately. Any supplements used are produced by reputable organisations and most of them have been part of the treatment routine for several years. The aims of the study is to evaluate improvement during and after treatment and to identify predictors of recovery. The goal is to understand the process of recovery with the long term goal to improve care given at the clinic.

Aim and research question

The first aim is to investigate improvement in symptom burden and health related quality of life during and after treatment (does symptom burden and health related quality of improve during treatment and are improvements stable at the 2 year follow-up?) The second aim is to investigate factors that predict recovery (Do persons with a high level of motivation for behavioural change experience a better improvement in symptom burden and health related quality of life than persons with a low level of motivation for behavioural change?).

Methods

Study population and inclusion criteria

All Swedish speaking patients (\>1= 18 years) visiting the clinic will be asked to participate in the study by clinic personnel when visiting the clinic. All patients at the clinic are able to provide informed consent and to fill out online forms.

Procedure

This is an observational study where patients are followed over time in terms of symptom burden and health related quality of life. The study participants are asked to fill out forms once a month for one year counting from the first visit, and once again 2 years after baseline. Clinical data is collected from the medial record by the clinician at the end of the study.

Questionnaires

(Jylhä 2009)(K, S et al. 2003)(Westerlund, Brandt et al. 2014)(Smets, Garssen et al. 1995)(Andreasson, Wicksell et al. 2016)(Spitzer, Kroenke et al. 2006)(Spitzer, Kroenke et al. 1999)

Clinical variables

Information on diagnosis, number of visits, tests and test results, treatment programme and background information (including age, gender, lifestyle factors, readiness for change, education, occupation, social support, height and weight, blood pressure), will be collected from the medical record of the patient by the clinician at the end of the study period.

Statistics

Based on experience of these types of analyses, 150 participants would give a reasonable foundation for the statistical analyses. 300 unique patients are expected to enrol during the study inclusion period and expect 200 of these to complete at least the first year of data collection. In the main analysis of the first aim, the effect of time on questionnaire scores will be investigated using mixed effect linear regression to see to what extent symptom burden and health related quality of life is affected during treatment and to investigate the stability in any improvements. Secondly, it will be investigated it a high adherence to the treatment programme is associated with improvement. Thirdly, the level of adherence to the treatment programme will be compared between patients with predominant abdominal symptoms and patients with predominant fatigue.

In the main analysis of the second aim, readiness for change will be tested as a moderator of the effect of time on questionnaire scores. Secondly, the level of improvement will be compared between patients who self-fund the treatment programme and patients with funding from employer or health insurance.

Patients often present with a range of different symptoms. Principal component analysis will be performed in an exploratory analysis to investigate if there are subgroups within the patient population, and if these subgroups differ in terms of treatment response. Covariation over time of symptoms, health related quality of life and self-rated health will be investigated in exploratory analyses.

Ethical considerations

The present study poses little risk to the participant. The treatment programme that the participant would undergo independently of the study is considered safe with few and mild side effects such as rash. As part of the study the participant report health information on a web questionnaire. Health data is sensitive information and the same platform will be used as for all other data collected by the clinic for treatment. The platform that is used is certified safe (add information) and complies to the GDPR regulation.

Risk of missing serious diagnoses

When dealing with symptoms such as persistent fatigue there is a risk that serious conditions such as cancer might be missed. However, the risk is estimated as low as low as in primary care at a Vårdcentral. Our medical doctor is still active in primary health care in parallel to Nordic Clinic and has many years of experience. Most of the patients at Nordic Clinic have been thoroughly investigated in the primary care system before signing up as patients at Nordic Clinic. Should patients however present with symptoms that warrant the investigation of serious conditions like malignancies, it is made sure that a thorough investigation has indeed been performed. If it has not, our medical doctor refers them back to primary or specialist health care.

Importance

There has not been a strong research tradition to evaluate treatment programmes based on functional medicine, albeit the individual components therein have all been evaluated and are found to be safe. However, all treatments given to patients need continuing evaluation. This two-year observational study will provide information regarding treatment outcomes and stability thereof over time, in addition to identifying patient groups that get the most benefit of the treatment. Future randomised controlled trials are needed to evaluate the effectiveness of the treatment programme.

Eligibility criteria: Inclusion Criteria:

* All Swedish speaking patients (\>/= 18 years) visiting the clinic will be asked to participate in the study by clinic personnel when they are visiting the clinic. All patients at the clinic are able to provide informed consent and to fill out online forms.

Exclusion Criteria:

* \<18 years, non-Swedish speaking

Primary outcomes:
measure: Change in gastrointestinal discomfort from baseline as assessed by the Gastrointestinal Symptom Rating Scale for IBS questionnaire (GSRS-IBS)
timeFrame: Baseline (time of enrollment), then each month 1-12 months after baseline, and then at 24 months.
measure: Change in fatigue from baseline as assessed by the Multidimensional Fatigue Inventory
timeFrame: Baseline (time of enrollment), then each month 1-12 months after baseline, and then at 24 months.
measure: Change in health-related quality of life from baseline as assessed by the 36-Item Short Form Health Survey (SF-36)
timeFrame: Baseline (time of enrollment), then each month 1-12 months after baseline, and then at 24 months.
measure: Change in sleep from baseline as assessed by the Karolinska Sleep Questionnaire (KSQ)
timeFrame: Baseline (time of enrollment), then each month 1-12 months after baseline, and then at 24 months.
measure: Change in anxiety from baseline as assessed by the Generalised Anxiety Disorder 7-item scale (GAD-7)
timeFrame: Baseline (time of enrollment), then each month 1-12 months after baseline, and then at 24 months.
measure: Change in presence or severity of depression from baseline as assessed by the Patient Health Questionnaire-9 (PHQ-9)
timeFrame: Baseline (time of enrollment), then each month 1-12 months after baseline, and then at 24 months.
measure: Change in overall health from baseline as assessed by the Self-rated health questionnaire
timeFrame: Baseline (time of enrollment), then each month 1-12 months after baseline, and then at 24 months.
Secondary outcomes:
measure: Correlation between motivation for behavioral change and change in symptom burden and health-related quality of life
timeFrame: Baseline (time of enrollment), then each month 1-12 months after baseline, and then at 24 months.
measure: Predictability of the predominance of fatigue or abdominal-related symptomatology for adherence to the treatment programme
timeFrame: Baseline (time of enrollment), then each month 1-12 months after baseline, and then at 24 months.
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Nordic Clinic
Study officials:
affiliation: Nordic Clinic
name: Annie ML Pettersson, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andreasson A, Wicksell RK, Lodin K, Karshikoff B, Axelsson J, Lekander M. A global measure of sickness behaviour: Development of the Sickness Questionnaire. J Health Psychol. 2018 Sep;23(11):1452-1463. doi: 10.1177/1359105316659917. Epub 2016 Jul 24.
citation: Bryant PA, Trinder J, Curtis N. Sick and tired: Does sleep have a vital role in the immune system? Nat Rev Immunol. 2004 Jun;4(6):457-67. doi: 10.1038/nri1369. No abstract available.
citation: Hallgren M, Stubbs B, Vancampfort D, Lundin A, Jaakallio P, Forsell Y. Treatment guidelines for depression: Greater emphasis on physical activity is needed. Eur Psychiatry. 2017 Feb;40:1-3. doi: 10.1016/j.eurpsy.2016.08.011. Epub 2016 Nov 10. No abstract available.
citation: Jylha M. What is self-rated health and why does it predict mortality? Towards a unified conceptual model. Soc Sci Med. 2009 Aug;69(3):307-16. doi: 10.1016/j.socscimed.2009.05.013. Epub 2009 Jun 10.
citation: Wiklund IK, Fullerton S, Hawkey CJ, Jones RH, Longstreth GF, Mayer EA, Peacock RA, Wilson IK, Naesdal J. An irritable bowel syndrome-specific symptom questionnaire: development and validation. Scand J Gastroenterol. 2003 Sep;38(9):947-54. doi: 10.1080/00365520310004209.
citation: Rezaie A, Pimentel M, Rao SS. How to Test and Treat Small Intestinal Bacterial Overgrowth: an Evidence-Based Approach. Curr Gastroenterol Rep. 2016 Feb;18(2):8. doi: 10.1007/s11894-015-0482-9.
citation: Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res. 1995 Apr;39(3):315-25. doi: 10.1016/0022-3999(94)00125-o.
citation: Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA. 1999 Nov 10;282(18):1737-44. doi: 10.1001/jama.282.18.1737.
citation: Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-7. doi: 10.1001/archinte.166.10.1092.
citation: Westerlund A, Brandt L, Harlid R, Akerstedt T, Lagerros YT. Using the Karolinska Sleep Questionnaire to identify obstructive sleep apnea syndrome in a sleep clinic population. Clin Respir J. 2014 Oct;8(4):444-54. doi: 10.1111/crj.12095.
citation: Younge JO, Gotink RA, Baena CP, Roos-Hesselink JW, Hunink MG. Mind-body practices for patients with cardiac disease: a systematic review and meta-analysis. Eur J Prev Cardiol. 2015 Nov;22(11):1385-98. doi: 10.1177/2047487314549927. Epub 2014 Sep 16.