Compassion and Metacognition Based Therapy for Schizotypal Personality Disorder: A Pilot Non-inferiority Randomized Controlled Trial on Repeated Measures.
Phase: NA
Conditions: Schizotypal Personality Disorder
Sponsor: Tages Onlus

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Trial Title:  Compassion and Metacognition Based Therapy for Schizotypal Personality Disorder: A Pilot 
Non-inferiority Randomized Controlled Trial on Repeated Measures. 
Internal Reference Number / Short title: Compassion and Metacognition in Schizotypal Personality ( 
CMBT ) 
Ethics Ref: 032020-07072020 
Date and Version No: 01-2021-02-11 
 
Chief Investigator: 
Simone Cheli 
Tages Onlus  
Telephone: +393285642442 
Email: simone.cheli@tagesonlus.org 
Investigators:  
Gil Goldzweig, The Academic College of Tel Aviv Yaffo, Tel Aviv, Israel 
Veronica Cavalletti, Tages Onlus, Firenze, Italy  
Cecilia Trevisani, Tages Onlus, Firenze, Italy  
 
Sponsor:  
Tages Onlus 
Via della Torretta, 14, Florence, Italy 
Funder:  
None 
 
 
Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone other than the 
Sponsor, the Investigator Team, HRA, host organisation, and members of the Research Ethics Committee 
and Regulatory Authorities unless authorised to do so. 
 
 
 

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TABLE OF CONTENTS 
 
1. 
KEY TRIAL CONTACTS ............................................................................................................................. 3 
2. 
BRIEF SUMMARY ................................................................................................................................... 4 
3. 
SYNOPSIS ............................................................................................................................................... 4 
4. 
ABBREVIATIONS ..................................................................................................................................... 5 
5. 
BACKGROUND AND RATIONALE ............................................................................................................ 7 
6. 
OBJECTIVES AND OUTCOME MEASURES ............................................................................................... 8 
7. 
TRIAL DESIGN ......................................................................................................................................... 8 
8. 
PARTICIPANT IDENTIFICATION .............................................................................................................. 9 
8.1. 
Trial Participants ............................................................................................................................ 9 
8.2. 
Inclusion Criteria ............................................................................................................................ 9 
8.3. 
Exclusion Criteria ........................................................................................................................... 9 
9. 
TRIAL PROCEDURES ............................................................................................................................... 9 
9.1. 
Recruitment ................................................................................................................................... 9 
9.2. 
Screening and Eligibility Assessment ............................................................................................. 9 
9.3. 
Informed Consent ........................................................................................................................ 10 
9.4. 
Randomisation ............................................................................................................................. 10 
9.5. 
Blinding and code-breaking ......................................................................................................... 10 
9.6. 
Early Discontinuation/Withdrawal of Participants ...................................................................... 10 
9.7. 
Definition of End of Trial ............................................................................................................. 11 
10. 
TRIAL INTERVENTIONS ..................................................................................................................... 11 
10.1. 
Interventions’ Description ....................................................................................................... 11 
11. 
SAFETY REPORTING ......................................................................................................................... 11 
11.1. 
Adverse Event Definitions ....................................................................................................... 11 
12. 
STATISTICS ....................................................................................................................................... 11 
12.1. 
Statistical Analysis Plan (SAP) .................................................................................................. 11 
12.2. 
Description of Statistical Methods .......................................................................................... 12 
12.3. 
Sample Size Determination ..................................................................................................... 12 
12.4. 
Analysis Populations ........................................................... Errore. Il segnalibro non è definito. 
12.5. 
Procedure for Accounting for Missing, Unused, and Spurious Data.Errore. Il segnalibro non è 
definito. 
12.6. 
Procedures for Reporting any Deviation(s) from the Original Statistical PlanErrore. 
Il 
segnalibro non è definito. 
13. 
DATA MANAGEMENT ...................................................................................................................... 12 

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13.1. 
Source Data ............................................................................................................................. 12 
13.2. 
Access to Data ......................................................................................................................... 12 
13.3. 
Data Recording and Record Keeping .................................. Errore. Il segnalibro non è definito. 
14. 
QUALITY ASSURANCE PROCEDURES ............................................................................................... 12 
14.1. 
Risk assessment ....................................................................................................................... 12 
14.2. 
Monitoring ............................................................................................................................... 13 
14.3. 
Trial committees ...................................................................................................................... 13 
14.3.1 Safety Monitoring Committee .................................................................................................. 13 
15. 
PROTOCOL DEVIATIONS .................................................................................................................. 13 
16. 
SERIOUS BREACHES .................................................................... Errore. Il segnalibro non è definito. 
17. 
ETHICAL AND REGULATORY CONSIDERATIONS ............................................................................... 13 
17.1. 
Declaration of Helsinki............................................................................................................. 13 
17.2. 
Guidelines for Good Clinical Practice ...................................................................................... 13 
17.3. 
Approvals ................................................................................................................................. 13 
17.4. 
Other Ethical Considerations .............................................. Errore. Il segnalibro non è definito. 
17.5. 
Reporting ................................................................................................................................. 14 
17.6. 
Participant Confidentiality ....................................................................................................... 14 
17.7. 
Expenses and Benefits ........................................................ Errore. Il segnalibro non è definito. 
18. 
FINANCE AND INSURANCE .............................................................................................................. 14 
18.1. 
Funding .................................................................................................................................... 14 
18.2. 
Insurance ................................................................................................................................. 14 
18.3. 
Contractual arrangements ................................................. Errore. Il segnalibro non è definito. 
19. 
PUBLICATION POLICY ....................................................................................................................... 14 
20. 
REFERENCES .................................................................................................................................... 14 
21. 
APPENDIX A:  CONSENT FORM ........................................................................................................ 17 
 
1. KEY TRIAL CONTACTS 
 
Chief Investigator 
Simone Cheli 
Telephone: +393285642442 
Email: simone.cheli@tagesonlus.org 
Sponsor 
Tages Onlus  

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Phone: 055 679037 
Email: info@tagesonlus.org 
Funder(s) 
None 
 
Clinical Trials Unit 
Veronica Cavalletti – Tages Firenze (Florence, Italy) 
Cecilia Trevisani – Tages Bologna (bologna, Italy) 
Statistician 
Gil Goldzweig – The Academic College of Tel Aviv Yaffo - Israel 
 
Committees 
Francesco Velicogna – Tages Onlus, Florence, Italy 
 
 
2. BRIEF SUMMARY  
The purpose of this study is to assess the safety and efficacy of a newly developed psychotherapy for 
schizotypal personality disorder. This new form of psychotherapy integrates compassion focused therapy 
and metacognitively oriented psychotherapy.  
3. SYNOPSIS 
 
Trial Title 
Compassion and Metacognition Based Therapy for Schizotypal Personality 
Disorder: A Pilot Non-inferiority Randomized Controlled Trial on Repeated 
Measures. 
Internal ref. no. (or 
short title) 
Compassion and Metacognition in Schizotypal Personality ( CMBT ). 
Trial registration 
Unique Protocol ID: 03-07072020 
Sponsor  
Tages Onlus  
Via della Torretta, 14, Florence, Italy 
Funder  
N/A  
Clinical Phase  
Recruiting  
Trial Design 
Parallel Assignment 
Randomized Controlled Trial with Repeated Measures 
Trial Participants 
Minimum Age: 18 Years 
Being diagnosed with Schizotypal Personality Disorder at SCID-5-AMPD 
Sample Size 
14 
Planned Trial Period  
Total lenght: December 15, 2020 - December 20, 2021  

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Pre-post evaluation between pre-assessment (1-month before the 
intervention) and 1 month follow-up. 
 
Planned Recruitment 
period  
December 15, 2020 - September 30, 2021 
 
Objectives 
Outcome Measures 
Timepoint(s)  
Primary 
 
 
 
Personality pathology: 
Total score at PID-5-BF 
 
 (i) at 1 month 
before 
intervention 
starts; (ii) once 
the 
treatment 
starts; (iii) 6 
measurements at 
the end of each 
month 
of 
intervention; 
at 
1-month follow-
up. 
Secondary 
 
 
 
Schizotypal 
Personality 
Disorder Diagnosis: 
Diagnosis 
at 
the 
3rd 
module 
of 
SCID-5-PD 
interview; 
General Psychopathology: 
Total score at SCL-90-R; 
Metacognition: 
Total score at MAS-A 
 
Pre-post 
evaluation 
between pre-
assessment (1-
month before 
the intervention) 
and 1-month 
follow-up 
assessment. 
 
Intervention(s) 
 
• 
IMP(s) 
 
• 
nIMP(s) 
 
 
• 
Other 
intervention(s)  
 
 
Compassion and Metacognition Based Therapy (CMBT): Third Wave 
Cognitive Therapy targeting metacognitive dysfuctions (through 
Metacognitively Oriented Psychotherapy) and selfcriticism (through 
Compassion Focused Therapy). 
6-month therapy, including 24 weekly sessions.   
Comparator  
Cognitive Behavioral Therapy: Standard Cognitive Behavioral Therapy for 
Personality Disorders plus Standard Psychopharmacological Treatment. 
6-month therapy, including 24 weekly sessions.   
 
4. ABBREVIATIONS 
 
 
AE 
Adverse event 
AR  
Adverse reaction 

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CBT 
Cognitive Behavioral Therapy 
CFT 
Compassion Focused Therapy 
CMBT-S 
Compassion and Metacognition Based Treatment for Schizotypal Personality Disorder 
CI 
Chief Investigator 
CRA 
Clinical Research Associate (Monitor) 
CRF 
Case Report Form 
CRO  
Contract Research Organisation 
CT 
Clinical Trials 
CTA 
Clinical Trials Authorisation 
CTRG 
Clinical Trials and Research Governance 
DMC/DMSC 
Data Monitoring Committee / Data Monitoring and Safety Committee 
DSUR 
Development Safety Update Report 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
GTAC 
Gene Therapy Advisory Committee 
HRA 
Health Research Authority 
IB 
Investigators Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IMP 
Investigational Medicinal Product 
IRB 
Independent Review Board 
MERIT 
Metacognitive Reflection and Insight Therapy 
MIT 
Metacognitive Interpersonal Therapy 
MHRA 
Medicines and Healthcare products Regulatory Agency 
NHS 
National Health Service 
RES 
 Research Ethics Service  
OXTREC 
Oxford Tropical Research Ethics Committee 
PI 
Principal Investigator 
PID-5-BF 
Personality Inventory for DSM-5,Brief Form 
PIL 
Participant/ Patient Information Leaflet 
R&D 
NHS Trust R&D Department 
REC 
Research Ethics Committee 
RSI 
Reference Safety Information  
SAE 
Serious Adverse Event 

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SAR 
Serious Adverse Reaction 
SCID-5-PD 
Structured Clinical Interview for DSM-5 Personality Disorders  
SCL-90-R 
Symptom Checklist – 90 – Revised  
SDV 
Source Data Verification 
SMPC 
Summary of Medicinal Product Characteristics 
SOP 
Standard Operating Procedure 
SPD 
Schizotypal Personality Disorder 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TMF 
Trial Master File 
TSG 
Oxford University Hospitals NHS Foundation Trust / University of Oxford Trials Safety 
Group 
 
5. BACKGROUND AND RATIONALE 
Schizotypal personality disorder (SPD) reflects a pervasive pattern of maladaptive behaviour, which has 
been suggested to involve either three or four different facets. These include positive features such as 
ideas of reference, magical thinking and suspiciousness; negative features such as anhedonia and lack of 
social interest; and cognitive features that involve disorganized thinking and impulsive nonconforming 
behaviour. SPD has been alternatively considered a personality disorder (PD), a subclinical form of 
schizophrenia or an expression of the liability for the development of schizophrenia. DSM-5 reports a 
prevalence of 4.6% in general population, with poor long-term outcomes, including significant 
impairments in social relationships, work and leisure activities, and a typical declining trajectory in overall 
functioning. Treatment options are scarce, and a systematic review published in 2018, reported just three 
psychosocial interventions for SPD. In the last three years, I acted as Principal Investigators of four studies 
aimed at outlining a novel, evidence-based intervention tailored for SPD. The general aim was to test an 
integrative psychotherapy rooted in metacognitively oriented psychotherapies and compassion focused 
therapy. A growing body of research suggests that many diagnosed with personality disorders and 
psychosis experience deficits in metacognition or the ability to form integrated ideas about themselves 
and others. They also struggle to regulate their brain’s evolved systems for decoding and responding to 
communication signals, and report a recurrent inability to regulate their arousal when facing internal (e.g. 
shame) and external (e.g. relations) stimula. Since SPD is a severe mental illness at the crossroads between 
personality disorder and psychosis, my colleagues and I suggest considering it from these deficits in 
metacognition and socially evolved systems. We tested how metacognition may be a primary target of a 
tailored psychotherapy. And we are recently exploring the role of compassion for one’s own distress, as a 
way to strengthen the ability to generate a self-soothing response to suffering. First, together with Paul 
Lysaker (Indiana University, Indianapolis) and Giancarlo Dimaggio (Center for Metacognitive Intepersonal 
Therapy, Rome) Dr. Simone Cheli (Tages Onlus) outlined and delivered a pilot study to test the suitability 
of a metacognitively oriented intervention for patients diagnosed with SPD (Cheli, Lysaker, Dimaggio, 
2019). Second, we tested a specifically designed assessment strategy for SPD integrating measures of 
metacognition, big five, alternative model of personality disorders (Cheli, 2020)). Third, together with 
Nicola Petrocchi (John Cabot University, Rome) and Veronica Cavaletti (Tages Onlus, Florence) we explored 
the suitability of online compassion focused therapy interventions for clients with recent early psychotic 
episodes (Cheli, Cavalletti, Petrocchi, 2020). Four, we recently concluded a study on a large sample of non-
clinical young adults (n=2234), aimed at exploring the moderating role of self-soothing and metacognition 
in the onset of a SPD. All these studies are seemingly supporting the need for a novel, integrative treatment 
for SPD, that is going to be test in randomized clinical trial. 

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In conclusion, the collected, even if partial, evidences and my clinical experience in treating SPD, may 
represent an opportunity for participants to better understand how to outline a treatment plan for an 
understudied area of psychopathology. 
6. OBJECTIVES AND OUTCOME MEASURES 
 
Objectives 
Outcome Measures  
Timepoint(s) 
of 
evaluation of this 
outcome measure 
(if applicable) 
Primary Objective 
To compare the effect of the CMBT-
S versus CBT plus standar 
psychopharmacotherapy for SPD. 
 
• 
Change in Personality pathology: 
Total score at PID-5-BF 
• 
Schizotypal Personality Disorder 
Diagnosis: Diagnosis at the 3rd 
module of SCID-5-PD interview; 
• 
General Psychopathology: Total 
score at SCL-90-R; 
• 
Metacognition: Total score at 
MAS-A 
 
 
9 
measurements: 
(i) 
at 
1 
month 
before intervention 
starts; (ii) once the 
treatment 
starts; 
(iii) 6 
measurements 
at 
the end of each 
month 
of 
intervention; at 1-
month follow-up; 
Pre-post evaluation 
between 
pre-
assessment 
(1-
month before the 
intervention) and 1-
month follow-up 
assessment. 
Secondary Objectives 
To assess the safety of CMBT-S in 
patients diagnosed with SPD 
• 
Dropout rate 
• 
Completion rate  
• 
Adverse 
events 
(suicidal 
behaviors, self-harm, psychotic 
episodes) rate 
At the end of the 
intervention: 
dropout rate (≤10% 
of 
subjects), 
completion 
rate 
(≤10% of sessions 
skipped), 
adverse 
event rate ((≤10% 
of subjects). 
7. TRIAL DESIGN 
Randomized Controlled Trial with Repeated Measures.  
After being informed about the study and potential risks, all patients giving written informed consent will 
undergo a psychological assessment so as to determine eligibility for study entry. Patients who meet the 
eligibility requirements will be randomized in a double-blind manner in a 1:1 ratio to new integrative 

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psychotherapy or treatment as usual (cognitive behavioral therapy plus standard psychopharmacological 
treatment). One month after the conclusion of the two forms of treatment (both lasting 6 months), 
patients will have access to the final follow-up assessment. 
8. PARTICIPANT IDENTIFICATION 
8.1. Trial Participants 
Participants with being diagnosed with Schizotypal Personality Disorder at SCID-5-AMPD with minimun 
age 18 years.  
8.2. Inclusion Criteria 
• 
Participant is willing and able to give informed consent for participation in the trial. 
• 
Male or Female, aged 18 years or above. 
• 
Diagnosed with Schizotypal Personality Disorder at SCID-5-AMPD. 
 
8.3. Exclusion Criteria 
The participant may not enter the trial if ANY of the following apply: 
• 
Being under psychotherapy or psychopharmacological treatment 
• 
Being diagnosed with schizophrenia and other psychotic disorders 
• 
Being diagnosed with bipolar disorder 
• 
Being diagnosed with intelletual disability 
• 
Being diagnosed with any neurological diseases 
9. TRIAL PROCEDURES 
9.1. Recruitment 
The recruitment centers were selected on the basis of their expertise in treating personality disorders and 
the presence of a multidisciplinary team. Subjects who during epidemiological studies or clinical 
assessment procedures report a diagnosis of SPD are approached and asked for their willingness to receive 
a subsequent assessment for possible entry into the study. Once the informed consent has been read and 
signed, the inclusion and exclusion criteria for the participants are confirmed. Finally, eligible subjects are 
randomized through software and assigned to treatment.  
9.2. Screening and Eligibility Assessment 
An assessment psychologist and a psychiatrist conduct an in-depth assessment of demographic and 
anamnestic variables and integrate them with the results of psychometric tests and structured interviews. 

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The maximum time between the assessment, the randomization and the start of the course is one month. 
Protocol waivers are not permitted.  
9.3. Informed Consent 
The participanta must personally sign and date the latest approved version of the Informed Consent form 
before any trial specific procedures are performed. 
Written and verbal versions of the Participant Information and Informed Consent will be presented to the 
participants detailing no less than: the exact nature of the trial; what it will involve for the participant; the 
implications and constraints of the protocol; the known side effects and any risks involved in taking part. 
It will be clearly stated that the participant is free to withdraw from the trial at any time for any reason 
without prejudice to future care, without affecting their legal rights and with no obligation to give the 
reason for withdrawal. 
The participant will be allowed as much time as wished to consider the information, and the opportunity 
to question the Investigator, their GP or other independent parties to decide whether they will participate 
in the trial. Written Informed Consent will then be obtained by means of participant dated signature and 
dated signature of the person who presented and obtained the Informed Consent. The person who 
obtained the consent must be suitably qualified and experienced, and have been authorised to do so by 
the Chief/Principal Investigator. A copy of the signed Informed Consent will be given to the participant. 
The original signed form will be retained at the trial site. 
9.4. Randomisation 
A simple computer will generate random number for each participant. CRO will design the randomization 
schedule and will hold the allocation blind to all the investigators.    
9.5. Blinding and code-breaking 
Participant, Care Provider, Outcomes Assessor are blinded to the allocation.  
9.6. Early Discontinuation/Withdrawal of Participants  
During the course of the trial a participant may choose to withdraw early from the trial treatment at any 
time.  This may happen for a number of reasons, including but not limited to:   
• 
The occurrence of what the participant perceives as an intolerable AE.   
• 
Inability to comply with trial procedures  
• 
Participant decision  
 
Participants may choose to stop treatment and/or study assessments but may remain on study follow-up.  
Participants may also withdraw their consent, meaning that they wish to withdraw from the study 
completely. Participants can withdraw completely from the study and withdraw the data and samples 
collected up until the point of withdrawal. The data and samples already collected would not be used in 
the final study analysis. (Any limits to this type of withdrawal where, for example analysis of their data or 
samples has already been integrated into interim results or dose escalation decisions etc. should be 
explained in the participant information sheet).   

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9.7. Definition of End of Trial 
The end of trial is the point at which all the data has been entered and queries resolved.  
10. TRIAL INTERVENTIONS  
10.1. 
Interventions’ Description 
Cognitive Behavioral Therapy Standard Cognitive Behavioral Therapy for Personality Disorders. 
Compassion and Metacognition Based Therapy: the intervention is a Third Wave Cognitive Therapy 
targeting metacognitive dysfuctions (through Metacognitively Oriented Psychotherapy) and selfcriticism 
(through Compassion Focused Therapy). 
Both treatments last 6 months.  
11. SAFETY REPORTING 
11.1. 
Adverse Event Definitions 
Adverse Event (AE) 
Any untoward medical occurrence in a participant to whom the 
intervention has been administered, including occurrences which are 
not necessarily caused by or related to that treatment. 
Serious 
Adverse 
Event 
(SAE) 
A serious adverse event is any untoward medical occurrence that: 
• results in death 
• is life-threatening 
• requires inpatient hospitalisation or prolongation of existing 
hospitalisation 
• results in persistent or significant disability/incapacity 
• consists of a congenital anomaly or birth defect*. 
Other ‘important medical events’ may also be considered a serious 
adverse event when, based upon appropriate medical judgement, the 
event may jeopardise the participant and may require medical or 
surgical intervention to prevent one of the outcomes listed above. 
NOTE: The term "life-threatening" in the definition of "serious" refers to 
an event in which the participant was at risk of death at the time of the 
event; it does not refer to an event which hypothetically might have 
caused death if it were more severe. 
  
12. STATISTICS 
12.1. 
Statistical Analysis Plan (SAP) 

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Primary outcomes will be evaluated through repeated measures ANOVA. Statistical analyses and reporting 
will be conducted following CONSORT guidelines, with the primary analyses based on the ITT principle, 
which considered data from all participants whose baseline data were available. Multiple imputation will 
be adopted to estimate mid-assessment, post-treatment, and follow-up scores for noncompleters (e.g., 
those who had missed plus than 10% of sessions, or those who decline to participate in the TAU condition). 
Additionally, we will also conduct per-protocol (PP) analyses, which refers to inclusion in the analysis of 
only those patients who strictly adhered to the protocol. 
12.2. 
Sample Size Determination 
ANOVA: Repeated measures, within-between interaction has been conducted in order to a priori compute 
required sample size. As input we estimate (Cheli, 2020) an effect size f equal to 0.37 with a power (1-β err 
prob) equal to 0.95. Moreover, we considered 9 measurements with at leas a correlation among them 
equal to 0.50 (PID-5-BF reports a test-restest valuet greater than 0.70). This led to a total sample equal to 
12 (critical F= 2.0563726; actual power= 0.9785743). By considering at least 10% of withdrawal we  
 
13. DATA MANAGEMENT 
13.1. 
Source Data 
Source documents are where data are first recorded, and from which participants’ CRF data are obtained. 
These include, but are not limited to, personal records (from which mental health history and previous 
treatment may be summarised into the CRF), clinical and office charts, laboratory and pharmacy records, 
diaries, microfiches, radiographs, and correspondence. 
CRF entries will be considered source data if the CRF is the site of the original recording (e.g. there is no 
other written or electronic record of data).  All documents will be stored safely in confidential conditions. 
On all trial-specific documents, other than the signed consent, the participant will be referred to by the 
trial participant number/code, not by name. 
13.2. 
Access to Data 
Direct access will be granted to authorised representatives from the Sponsor, host institution and the 
regulatory authorities to permit trial-related monitoring, audits and inspections. 
14. QUALITY ASSURANCE PROCEDURES 
14.1. 
Risk assessment  
The trial will be conducted in accordance with the current approved protocol, GCP, relevant regulations 
and standard operating procedures. A risk assessment and monitoring plan will be prepared before the 
study opens and will be reviewed as necessary over the course of the trial to reflect significant changes to 
the protocol or outcomes of monitoring activities.  

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14.2. 
Monitoring  
Regular monitoring will be performed. Data will be evaluated for compliance with the protocol and 
accuracy in relation to source documents. Following written standard operating procedures, the monitors 
will verify that the clinical trial is conducted and data are generated, documented and reported in 
compliance with the protocol, GCP and the applicable regulatory requirements. 
14.3. 
Trial committees 
14.3.1 Safety Monitoring Committee 
Tages Onlus will conduct a review of all SAEs for the trial reported during the quarter and cumulatively. 
The aims of this committee include: 
• 
To pick up any trends, such as increases in un/expected events, and take appropriate action 
• 
To seek additional advice or information from investigators where required 
• 
To evaluate the risk of the trial continuing and take appropriate action where necessary 
 
15. PROTOCOL DEVIATIONS  
A trial related deviation is a departure from the ethically approved trial protocol or other trial document 
or process (e.g. consent process or IMP administration) or from Good Clinical Practice (GCP) or any 
applicable regulatory requirements. Any deviations from the protocol will be documented in a protocol 
deviation form and filed in the trial master file. 
16. ETHICAL AND REGULATORY CONSIDERATIONS 
16.1. 
Declaration of Helsinki 
The Investigator will ensure that this trial is conducted in accordance with the principles of the Declaration 
of Helsinki. 
16.2. 
Guidelines for Good Clinical Practice 
The Investigator will ensure that this trial is conducted in accordance with relevant regulations and with 
Good Clinical Practice. 
16.3. 
Approvals 
Following Sponsor approval the protocol, informed consent form, participant information sheet will be 
submitted to an appropriate Research Ethics Committee (REC), HRA (where required), regulatory 
authorities (MHRA in the UK), and host institution(s) for written approval. 
The Investigator will submit and, where necessary, obtain approval from the above parties for all 
substantial amendments to the original approved documents. 

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16.4. 
Reporting 
The CI shall submit once a year throughout the clinical trial, or on request, an Annual Progress Report to 
the REC, host organisation, funder (where required) and Sponsor.  In addition, an End of Trial notification 
and final report will be submitted to the REC, host organisation and Sponsor. 
16.5. 
Participant Confidentiality 
The study will comply with the General Data Protection Regulation (GDPR) and Data Protection Act 2018, 
which require data to be de-identified as soon as it is practical to do so. The processing of the personal 
data of participants will be minimised by making use of a unique participant study number only on all study 
documents and any electronic database(s), with the exception of the CRF, where participant initials may 
be added.  All documents will be stored securely and only accessible by study staff and authorised 
personnel. The study staff will safeguard the privacy of participants’ personal data. 
17. FINANCE AND INSURANCE 
17.1. 
Funding 
Tages Onlus will be the only institution financially supporting the study. 
17.2. 
Insurance 
 
Tages Onlus and single therapists are legally liable for the negligent acts and omissions of their 
employees. If participants are harmed whilst taking part in a clinical trial as a result of negligence on the 
part of a member of the trial team this liability cover would apply. In exceptional circumstances an ex-
gratia payment may be offered. 
 
18. PUBLICATION POLICY 
IPD will be released at the end of the study and will be accessible permanently. 
Individual partecipants data underline the results in all the future publications related to the trial will be 
available after deidentification. 
 
19. REFERENCES 
 
Balaratnasingam S, Janca A. Normal personality, personality disorder and psychosis: current views and 
future perspectives. Curr Opin Psychiatry. 2015 Jan;28(1):30-4. doi: 10.1097/YCO.0000000000000124. 
Review. PubMed 25415496 
 
Bora E. Theory of mind and schizotypy: A meta-analysis. Schizophr Res. 2020 Aug; 222:97-103. doi: 
10.1016/j.schres.2020.04.024. Epub 2020 May 25. Review. PubMed 32461089 
 

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Braehler C, Gumley A, Harper J, Wallace S, Norrie J, Gilbert P. Exploring change processes in compassion 
focused therapy in psychosis: results of a feasibility randomized controlled trial. Br J Clin Psychol. 2013 
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20. APPENDIX A:  CONSENT FORM 
 
CENTER FOR PSYCHOLOGY AND HEALTH – TAGES CHARITY 
CONSENT TO BE PART OF A RESEARCH STUDY  
 
1.  KEY INFORMATION ABOUT THE RESEARCHERS AND THIS STUDY   
Study title:  
Principal Investigator: Simone Cheli, PsyD, Tages Charity 
Co-Investigator(s): Veronica Cavalletti, PsyD, Tages Charity; Cecilia Trevisani, PsyD, Tages 
Charity 
Faculty Advisor: Francesco Velicogna, PsyD, Tages Charity 
 
 
You are invited to take part in a research study.  This form contains information that will help you 
decide whether to join the study.  
Taking part in this research project is voluntary. You do not have to participate and you can stop 
at any time. Please take time to read this entire form and ask questions before deciding whether 
to take part in this research project. 
2. PURPOSE OF THIS STUDY 
People who are diagnosed with Schizotypic Personality Disorder have difficulty finding adequate 
support to deal with the many problems resulting from this diagnosis. To date, there are no 
recognized guidelines for psychotherapeutic treatments. Tages Charity has developed over the 
last few years a new form of psychotherapy that complements existing evidence-based protocols. 
The goal of this study is to evaluate the effectiveness of this new form of psychotherapy by 
comparing it with one that has shown excellent evidence in other forms of personality disorders. 
 
3. WHO CAN PARTICIPATE IN THE STUDY 
3.1 Who can take part in this study?  

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People over the age of 18 who have received a diagnosis of SPD can participate in the study. It 
was decided to exclude people who in addition to this diagnosis have received a diagnosis related 
to the schizophrenic spectrum and neurological disorders. This decision is linked to the fact that 
we have preliminarily tested the new intervention on people with only the diagnosis of SPD and 
we do not want to expose the participants to potentially useless interventions. 
 
4.  INFORMATION ABOUT STUDY PARTICIPATION 
4.1 What will happen to me in this study? 
People who agree to participate in the study, after talking with the researchers to get all the 
information they require and having signed the informed consent, will access the following path: 
 
1) They will carry out an interview with a psychologist expert in diagnosis who will evaluate if the 
person corresponds to the characteristics of inclusion and exclusion. If the person is not eligible, 
he will be explained why and if he requests it, he will be able to access another psychotherapy 
path within the Tages Centers. 
2) The people who are eligible will instead enter a process called "randomization". This purpose 
is to assign people to one of the two interventions (the new one being validated and the standard 
one for other personality disorders) through a computerized procedure. The purpose of this 
procedure is not to influence the results with personal choices of the researchers or a priori 
evaluations of the participants. 
3) Within one month of the admission assessment, participants will begin the psychotherapy 
course which will consist of a weekly session of 50-60 minutes with the assigned therapist. The 
duration of the psychotherapy course is 6 months for a total of 24 sessions. During the interviews 
the participants will be invited to talk about their problems and their life experiences, as well as to 
experiment with new coping strategies inside and outside the session. 
4) At the end of each month of psychotherapy, participants will be asked to fill in questionnaires 
to assess their psychological well-being. Similarly, one month after the end of the intervention, the 
participants will have an interview and a final assessment with the same psychologist who 
conducted the entrance assessment. 
 
4.2 How much of my time will be needed to take part in this study?  
The study has a total duration of 8 months. In the first month, people will only have to take part in 
the initial assessment lasting about 2 hours. Thereafter, the 6-month psychotherapy course will 
begin (24 weekly sessions, each lasting a maximum of 1 hour). Finally, one month after the 
conclusion of the psychotherapy there will be a final assessment lasting about 2 hours. 
 
4.3 If I decide not to take part in this study, what other options do I have?  

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Participants can withdraw from the study at any time. If available, researchers will be interested in 
understanding the reasons and offering the possibility of accessing an alternative psychotherapy 
path to that offered (outside the study). 
 
 
5.  INFORMATION ABOUT STUDY RISKS AND BENEFITS 
5.1 What risks will I face by taking part in the study?  What will the researchers do to protect 
me against these risks? 
Pathways of diagnostic evaluation or psychological or psychotherapeutic intervention can expose 
people to denied and unpleasant experiences. The objective of an intervention is in fact to 
understand the ways that generate suffering and develop alternative strategies. During this 
process, people can come into contact with disturbing emotions, thoughts and feelings related to 
the past or the present. 
Although this is the purpose of psychotherapy and therapists have experience in this area, people 
may find some experiences intolerable. If so, they can first discuss it with their therapist, seek 
advice from the project manager who is a psychologist who is experienced with these issues, or 
ask to stop the intervention. 
 
Because this study collects information about you, one of the risks of this research is a loss of 
confidentiality. See Section 8 of this document for more information on how the study team will 
protect your confidentiality and privacy. 
 
 
5.2 How could I benefit if I take part in this study?  How could others benefit?   
You may not receive any personal benefits from being in this study. However, others may benefit 
from the knowledge gained from this study. Existing data suggest that you might benefit from a 
psychotherapy, in terms both of an increase awareness of your ways of thinking and behaving, 
and of a reduction of your distress. 
 
6.  ENDING THE STUDY 
6.1 If I want to stop participating in the study, what should I do? 
You are free to leave the study at any time.  If you leave the study before it is finished, 
there will be no penalty to you. If you decide to leave the study before it is finished, please 
tell one of the persons listed in Section 9. “Contact Information”. If you choose to tell the 
researchers why you are leaving the study, your reasons may be kept as part of the study 
record. The researchers will keep the information collected about you for the research 
unless you ask us to delete it from our records. If the researchers have already used your 
information in a research analysis it will not be possible to remove your information. 

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7.  FINANCIAL INFORMATION 
7.1 Will I be paid or given anything for taking part in this study? You will not receive any 
compensation for your participation in the study, with the sole exception of the psychotherapy 
intervention itself. 
 
7.1.1 Will I need to pay anything to be part of the study? To be part of the study, you will not 
need to pay for anything. 
 
7.2 Who could profit or financially benefit from the study results?  
The team’s member are paid for their activities by Tages Charity. Such institution does not receive 
any compensation or financial benefit for this research. 
 
8. PROTECTING AND SHARING RESEARCH INFORMATION  
 
8.1 How will the researchers protect my information? 
For the purposes of data analysis and publication, all data will be anonymised. Only three people 
will be able to associate your name and surname with the data collected: the psychologist who will 
give you the entry and final interview; the psychologist who will conduct his psychotherapy; the 
psychologist in charge of the study. As registered psychologists, they have a legal and ethical 
obligation not to disclose your data. Only the psychologist who will act as his psychotherapist will 
be able to associate what emerged in psychotherapy with his name. All data will be anonymised 
by the psychologist responsible for the study. 
 
8.2 Who will have access to my research records? 
No one other than the people listed in section 8.1 will be able to associate your data with your 
name. The anonymized data will instead be made available to research institutions that will request 
it after approval by the Ethics Committee of Tages Onlus. 
 
 
9. CONTACT INFORMATION 
Who can I contact about this study? 
 
Principal Investigator: Simone Cheli 

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Email: simone.cheli@tagesonlus.org 
Phone: +39 3285642442 
 
If you have questions about your rights as a research participant, or wish to obtain 
information, ask questions or discuss any concerns about this study with someone other 
than the researcher(s), please contact the following: 
Tages Onlus 
Via della Torretta 14, 50137 Firenze, Italy 
Telephone: +39 055 679037 
E-mail: info@tagesomlus.org  
 
 
10. YOUR CONSENT  
Consent/Assent to Participate in the Research Study 
By signing this document, you are agreeing to be in this study. Make sure you understand what 
the study is about before you sign. I/We will give you a copy of this document for your records and 
I/we will keep a copy with the study records.  If you have any questions about the study after you 
sign this document, you can contact the study team using the information in Section 9 provided 
above. 
 
I understand what the study is about and my questions so far have been answered. I agree to take 
part in this study.  
 
Print Legal Name: _____________________________________________________ 
 
Signature: ___________________________________________________________ 
 
Date of Signature (mm/dd/yy): ___________________________________________