Improving Vaccination in Older Adults by Inducing Autophagy With Spermidine

NCT05421546 | Completed

• 1 other identifier: R75468/RE001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Easing the morbidity and economic burden of age-related diseases is one of the major medical challenges. One of the key obstacles to healthy ageing is immune senescence, including the failure of lymphocytes to respond adequately to infection, malignancy and vaccination. Infectious diseases remain the fourth most common cause of death among the elderly in the developed world. Moreover, the gain of chronic low-grade non-specific inflammation with age contributes to many age-related diseases. Our early work showed that autophagy, the main cellular bulk degradation pathway in the cell, prevents ageing of the immune system. In preclinical models we showed an age-related decline in T cell autophagy. We rejuvenated the immune system by restoring autophagy in T and B cells with the autophagy-inducing metabolite spermidine. Here we are asking for matched funds for a small human clinical trial to confirm that spermidine has the same effect when administered to humans. We will give the nutraceutical spermidine to human volunteers aged \>65 years either during or after vaccination against SARS-CoV-2 or influenza to test improvement of vaccine responses, immune senescence and inflamm-aging. We will also confirm whether a novel pathway we discovered that links spermidine to autophagy operates in humans, allowing us to make more specific drugs in the future. This small study of 120 volunteers overall will pave the way for a larger clinical trial with spermidine or novel related drugs.

Conditions

COVID-19; Vaccine Reaction

Outcome Measures

Primary Outcomes (1)

• The primary objective of this study is to determine the safety of daily Spermidine supplements following the vaccine booster for Coronavirus (SARS-CoV-2) and its effects on antibody levels in older people, using validated assays.

  1. The safety of daily Spermidine supplements following the vaccine booster for Coronavirus (SARS-CoV-2). 2. The SARS-CoV-2 antibody levels in older people, using validated assays.

  37 weeks

Secondary Outcomes (1)

• Our secondary objective is to determine the effects of daily Spermidine supplements on the immune 'memory' response to Coronavirus vaccine and the booster in older people.

  37 weeks

Study Arms (2)

Spermidine arm

ACTIVE COMPARATOR

This arm will enrol 20 volunteers aged 65 years of age or older (65-90) who have received two doses of the Coronavirus vaccine, with the vaccination course completed more than 8 weeks before recruitment. Following a baseline venous blood sample, participants will receive Spermidine supplements 6mg/day and oral administration once daily. A research appointment and venous blood sample will be requested at the point of recruitment, 5 weeks, 13 weeks and 37 weeks after recruitment of the participant.

Dietary Supplement: Spermidine or Placebo

Placebo arm

PLACEBO COMPARATOR

This arm will enrol 20 volunteers aged 65 years of age or older (65-90) who have received two doses of the Coronavirus vaccine, with the vaccination course completed more than 8 weeks before recruitment. Following a baseline venous blood sample, participants will receive placebo oral administration once daily. A research appointment and venous blood sample will be requested at the point of recruitment, 5 weeks, 13 weeks and 37 weeks after recruitment of the participant.

Dietary Supplement: Spermidine or Placebo

Interventions

Spermidine or Placebo DIETARY_SUPPLEMENT

The supplement, Spermidine, is made mainly from wheatgerm and can be bought in health food shops. It is a powder that can be easily dissolved in water and taken as a drink. The 'placebo' is a sugar powder that can be similarly dissolved in water and taken as a drink.

Placebo arm; Spermidine arm

Eligibility Criteria

• Age: 65 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Participants must be 65 years old or more and must have the capacity to provide written consent after discussing the participant information sheet with a member of the clinical study team. Participants must have received 2 doses of the COVID vaccine and a booster dose.

You may not qualify if:

• Participants who are acutely unwell.
• Participants who have had a clear clinical history of COVID symptoms or a previous positive COVID PCR( polymerase chain reaction) swab or antibody test
• Participants who cannot provide informed written consent
• Participants who use systemic steroids for more than one week e.g prednisolone \>0.5mg/kg/day in the three months prior to first study intervention
• Chronic administration (≥14 days in total) of immunosuppressants or other immune modifying drugs in the 3 months prior to first study intervention
• Receipt of blood, blood products and/or plasma derivatives or any immunoglobulin preparation in the three months prior to first study intervention
• Participants who have been diagnosed with medical conditions that can suppress the immune system or diabetes
• Participants with previous allergy to or constituent parts of Spermidine supplements or who have gluten intolerance
• Participants already taking Spermidine supplements at the time of recruitment or for 6 months prior to recruitment to the study
• Participants that are in custody
• Participants that do not live in the UK
• Participants that are pregnant
• Participants who are shielding

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

University of Oxford

Oxford, United Kingdom

Location

MeSH Terms

Conditions

COVID-19

Interventions

Spermidine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Putrescine; Biogenic Polyamines; Biogenic Amines; Amines; Organic Chemicals; Polyamines

Study Officials

• Katja Simon, Prof.

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2022
• First Posted: June 16, 2022
• Study Start: August 1, 2022
• Primary Completion: August 31, 2023
• Study Completion: December 2, 2023
• Last Updated: May 9, 2024

Record last verified: 2022-08

Locations

GB (1)