Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Not authorised
Participants planned
60
Countries
1
Sites
1
Post-acute COVID syndrome(PACS) diagnosis.
The AIM 1 of the project is to compare two years lifestyles intervention alone or in association with metformin or rapamycin pulse therapy in changing aging trajectories depicted by by an improvement of physical performance assessed by SPPB score as continous variable in people with PACS.
Key facts
- Sponsor
- Azienda Ospedaliero Universitaria Di Modena
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Virus Diseases [C02]
- Decision date (initial)
- 2023-07-13
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Ministery of Health
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The AIM 1 of the project is to compare two years lifestyles intervention alone or in association with metformin or rapamycin pulse therapy in changing aging trajectories depicted by by an improvement of physical performance assessed by SPPB score as continous variable in people with PACS.
Secondary objectives 2
- The AIM 2 of the project is to verify whether a two years lifestyle intervention alone or in association with metformin or rapamycin pulse therapy could dampen inflammation and downregulate the Immune risk phenotype in people with PACS.
- The other secondary objective of the project is to compare safety and tolerability of a two years lifestyles intervention alone or in association with metformin or rapamycin pulse therapy in people with PACS.
Conditions and MedDRA coding
Post-acute COVID syndrome(PACS) diagnosis.
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 23.0 | PT | 10084268 | COVID-19 | 100000004862 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Gero-PACS This is a randomized, controlled, open label, clinical trial of phenotypically frail older male and female subjects 40-80 years of age with a confirmed PACS diagnosis.
|
Randomised Controlled | None | group 1: lifestyles intervention (unsupervised exercise-nutrition intervention, though a personalized counseling program provided by a dietician and a physical therapist) group 2: lifestyles intervention + two periods of 18 weeks metformin pulse therapy one year apart (metformin 1000 mg prolong release daily) at a daily dose established according to estimated glomerular filtration rate, in detail 1000 mg if eGFR>50 mil/min or 500 mg if eGFR between 49-30 mil/min. If during follow up glomerular filtration rate decrease <30 mil/min metformin will be stopped. group 3: lifestyles intervention + two periods of 18 weeks rapamycin pulse therapy one year apart (1mg/m2 daily). |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Confirmed PACS diagnosis according to WHO definition by two consecutive clinical assessment
- Previous hospital admission for Severe COVID Pneumonia
- Age 40-80 years
- Frailty or pre-frailty status performed with frailty phenotype criteria
- Independently mobile
- Able and willing to provide written consent.
Exclusion criteria 8
- Previous or current use of metformin
- Diabetes history or diagnosis at baseline
- Transplant or cancer requiring chemotherapy
- History of chronic kidney disease (eGFR<30 mil/min)
- Allergies to metformin or rapamycin
- Female participant pregnant or breastfeeding
- Baseline SPPB score <3
- Life expectancy <6 months
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 3
- Short Physical Performance Battery
- Frailty reversibility
- Quality of life assessed with EQ 5D-5L
Secondary endpoints 4
- Identification of the main changes in peripheral blood cells that identify the immune risk phenotype (CD4/CD8 T cell ratio, senescent/activated CD8+ T cells, number of B lymphocytes and NK cells)
- Evaluation of the change that occur in the plasma level of the main inflammatory and anti-inflammatory cytokines, chemokines and their receptors.
- Analysis of the differences in monocyte activation and phenotypes (inflammatory, classical, non classical) among groups
- The occurrence of adverse events (AEs), changes on clinical examination including vital signs and weight, and laboratory examinations (biochemistry, hematology and urinalysis)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
SUB10537MIG · Substance
- Active substance
- Sirolimus
- Pharmaceutical form
- ORAL SOLUTION
- Route of administration
- ORAL
- Max daily dose
- 1.00 mg/m2 milligram(s)/sq. meter
- Max total dose
- 1.00 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 36 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- for different therapeutic indications
SUB08831MIG · Substance
- Active substance
- Metformin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 1000 mg milligram(s)
- Max total dose
- 1000 mg milligram(s)
- Max treatment duration
- 36 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- for different therapeutic indications
SUB08831MIG · Substance
- Active substance
- Metformin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 500 mg milligram(s)
- Max total dose
- 500 mg milligram(s)
- Max treatment duration
- 36 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- for different therapeutic indications
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Azienda Ospedaliero Universitaria Di Modena
- Sponsor organisation
- Azienda Ospedaliero Universitaria Di Modena
- Address
- Largo Del Pozzo 71
- City
- Modena
- Postcode
- 41124
- Country
- Italy
Scientific contact point
- Organisation
- Azienda Ospedaliero Universitaria Di Modena
- Contact name
- Giovanni Guaraldi
Public contact point
- Organisation
- Azienda Ospedaliero Universitaria Di Modena
- Contact name
- Servizio Formazione, Ricerca e innovazione
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Not authorised | 60 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-03-30 | Italy | Not acceptable 2023-07-10
|
2023-07-13 |