Naturopathic-pharmacological Consultation on the Use of Dietary Supplements in Patients With Hematological Diseases
Phase: NA
Conditions: Hematologic Diseases
Sponsor: Bnai Zion Medical Center

Cover page: 
 
Official Title of the study: 
Naturopathic-pharmacological consultation on the use of dietary 
supplements in patients with hematological diseases 
 
 
Date: August 30th, 2023 
 
 

BACKGOUND: 
Dietary and herbal supplements (DHS) are used by over 50% of the general population 
and about 30% of patients with hematological diseases (1,2). DHS use involves safety 
issues related to lack of knowledge and regulation, as well as the risk of side effects and 
interactions with other DHS and drugs. Indeed, the prevalence of adverse events related 
to the use of DHS has been estimated at about 20% of DHS users (3-5). These are 
particularly relevant in patients receiving anticoagulants, chemotherapy, or biological 
drugs (6-8). On the other hand, DHS may improve various symptoms related to the 
disease or its treatment (2). For the above reasons, clear and evidence-based guidelines 
are required for the effective and safe use of DHS in patients with hematological 
conditions. At Bnai Zion Medical Center, a naturopathic-pharmacological clinical 
consultation service regarding the use of DHS has been installed in the hematological 
unit since 2018. The current study aims to examine the effect of such a clinical 
naturopathic-pharmacological counseling on the effectiveness and safety of the use of 
DHS in patients with hematological conditions. 
 
METHODS: 
Study setting: This is a cross-sectional study that will take place at the Hematology Unit 
of Bnai Zion Medical Center in Haifa, Israel. 
Ethics review: The study protocol was reviewed and approved by the Institutional 
Review Board in accordance with the Helsinki Declaration (0149-20-BNZ). 
Study population: Patients will be referred by the medical or nursing staff of the 
Hematology Unit at the Bnai Zion Medical Center according to inclusion criteria: (1) 
Followed up for a hematological condition; (2) Ability to fill simple questionnaires in 
Hebrew, Russian or Arabic; (3) Indication for consultation: (a) Patient's request to 
expand knowledge about the use of DHS, (b) Patient using DHS, (c) Patient's desire to 
start using DHS, (d) Patient that is interested in hearing about the use of DHS for his/her 
health condition, (e) Medical or nursing team's recommendation to take DHS for 
medical treatment or to improve compliance with conventional treatment. There are no 
exclusion criteria. After explanation and agreement to participate in the study, the 
patient will be asked to sign an informed consent form. 

Intervention: The naturopathic-pharmacological consultation includes a naturopath and 
a clinical pharmacist and will be recorded in the computerized system with a copy given 
to the patient, the attending hematologist, the naturopath, and the clinical pharmacist. 
It will consist of at least two meetings: 
First meeting: The patients will be asked to document the DHS that they use or intend 
to use, or the extent and interests they have in this regard. Socio-demographic and 
medical data will be recorded based on anamnesis and a look at the patient's chart, with 
an emphasis on regular medications (anticoagulants, chemotherapy) and compliance 
with treatment, and relevant laboratory results (blood count, coagulation) if necessary. 
A safety assessment will be performed based on the above data, by the clinical 
pharmacist, and with the help of scientific databases. An effectiveness assessment will 
be carried out by the naturopath and with the help of scientific databases. The meeting 
will conclude with a recommendation to start, stop, or continue treatment with certain 
DHS, and will be recorded in the computer system. 
Follow-up meetings: The second meeting will be held physically or digitally at least a 
week after the first meeting, and additional meetings will be held as needed, on the 
recommendation of the medical or nursing staff, the patient himself, the naturopath, or 
the clinical pharmacist. At these meetings, the safety and effectiveness of the 
supplements will be evaluated based on the patient's questionnaire and the effect on 
compliance with treatment with conventional drugs. 
Training and quality control: The naturopaths who will be involved in the consultation 
have at least 5 years of clinical experience among patients with oncological or haemato-
oncological conditions. The clinical pharmacist involved in the study has a third degree 
(PhD) in clinical pharmacy and specialized on dietary and herbal supplements. A Data 
Safety Monitoring Board constituted of five experts will control the safety, and quality 
of the intervention as well as data collection on a yearly basis. Dropout, withdrawal, 
treatment adherence and uncollected data will be recorded until completion of the study. 
Outcomes: 
Primary outcome: The primary outcome will be the safety of the use of DHS in 
patients with a hematological disease through naturopathic counseling. This will be 
documented by the number of potential interactions with moderate to major level of 
significance prevented by such consultation in each patient, as well as the incidence of 

DHS-related safety events. The Naranjo and modified FDA algorithm will be used to 
assess the causality of such events with the specific dietary supplements (9), and only 
side effects at least possibly caused by the DHS according to these scales will be 
considered. 
Secondary outcomes: 
The efficacy of the different prescribed DHS will be assessed by symptom relief as 
measured by the Measure Yourself Concerns and Wellbeing (MYCAW) questionnaire 
that will be filled at the first meeting before the consultation, and again at each meeting. 
The MYCAW questionnaire is appropriate due to its validity, translation into relevant 
languages, combination of both quantitative and qualitative data, and appropriateness 
to integrative medicine studies. 
Patient-physician communication around the use of DHS will be described before, 
during and after the series of consultations by asking the patient whether the topic has 
been brought up with the treating hematologist and checking the documentation of the 
use of DHS in the medical charts. 
Satisfaction of the patients will be evaluated by a direct question asked after each 
meeting ranking in a 1-5 Likert scale the satisfaction of the patient from the 
consultation. 
Compliance with hematological treatment will be calculated by the relative dose 
intensity (RDI) of the prescribed hematological drugs both before and after 
intervention. 
Finally, a qualitative evaluation of the staff and patients from naturopathic-
pharmacological counseling will be assessed. Indeed, semi-structured in-depth 
interviews will be conducted with patients who are interested in participating in the 
qualitative arm (10-15 patients) and the staff members involved (medical staff, nursing 
staff, naturopath, clinical pharmacist). The goal is to describe the process of building 
the naturopathic-pharmacological consultation and evaluate the satisfaction of the staff 
and patients in a qualitative manner, in order to complete the quantitative assessment 
that will be carried out in the consultation itself. 
Criteria for discontinuation: Participants may be discontinued from the study if they 
voluntary withdraw informed consent, for safety reasons or due to significant non-

compliance with the study protocol as judged by the Principal Investigator. Reasons for 
discontinuation will be recorded and patients withdrawn from the study will be included 
in the intention-to-treat analysis. 
Sample size calculation: Since the prevalence of DHS-related side effects has been 
estimated at 18% of DHS users in a previous study (5) and that DHS-drug interactions 
may cause about half of such side effects, we estimated that the prevalence of DHS-
related adverse events in patients undergoing naturopathic consultation will be about 
10%. Based on these data, we calculated the minimal sample size with Scalex and 
ScalaR calculators (10). With a level of confidence of 95% (alpha 5%), a precision of 
10% and an estimated prevalence of 10% of adverse events, we needed a minimum of 
35 patients in the study. 
Statistical methods: Data analysis will be performed using IBM SPSS Statistics 
software. Demographic and clinical data will be analyzed at baseline. Quantitative 
variables will be described using mean and standard deviation or median with range 
(minimum and maximum) depending on their distribution. Qualitative variables will be 
described using frequency and percentage distributions. For comparing normally 
distributed variables between recruitment and post-intervention, we will use the paired 
t-test. For comparing variables that do not distribute normally between the different 
time points, we will use the Mann-Whitney test. For comparing qualitative variables 
between time points, we will use the independent Chi-square test and Fisher exact test. 
All comparisons will be two-sided with significance level set at p<0.05. 
 
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