High Intensity Interval Training in the Treatment of Familial Hypercholesterolemia (UPPA-FH)

NCT06833944 | Not Yet Recruiting

• 1 other identifier: PID2022-142844OB-I00
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This study has one main objective: a) To assess the impact of two different supervised exercise interventions on cardiorespiratory fitness and markers of subclinical atherosclerosis in patients with Familiar Hipercolesterolemia (FH), and to unravel the underlying mechanisms behind these effects. The starting hypothesis of the UPPA-FH project anticipates that both exercise interventions will produce a large increase in cardiorespiratory fitness and will improve significant markers of atherosclerosis in patients with FH, with high-intensity interval training program (HIIT) being more efficient than the moderate-intensity continuous training (MICT) modality. The main effects will be mediated by a significant change in the metabolomic signature of the participants. In addition, higher physical activity will be associated with more favorable markers of atherosclerosis progression, as shown through blood and image technique

Conditions

Familiar Hypercholesterolemia

Keywords

Inflamation markers; Cardiovascular risk; Physical fitness; Exercise; Cardiovascular disease; LDL cholesterol

Outcome Measures

Primary Outcomes (1)

• Cardiorespiratory fitness

  It will be evaluated using the Bruce Protocol Ramp, variation of the most widely used protocol in cardiology units worldwide (Bruce Protocol). The test is performed on a treadmill, where the speed and incline will gradually increase every 15 seconds until exhaustion. Because CRF is the primary study outcome, the maximum oxygen uptake will be continuously measured with the Vyntus CPT (see budget). A 12-lead ECG will be used to monitor heart rhythm and blood pressure will also be monitored. The rating of perceived exertion (RPE, Borg scale 1-10), maximum heart rate (bpm at exhaustion) and recovery heart rate and blood pressure (1 and 3 minutes later, bpm) will be recorded.

  Before and after the training intervention or control (16 weeks).

Secondary Outcomes (63)

• Vascular inflammation

  Before and after the training intervention or control (16 weeks).

• Arterial Stiffness

  Before and after the training intervention or control (16 weeks).

• Carotid Doppler Ultrasound

  Before and after the training intervention or control (16 weeks).

• Physical activity

  Before and after the training intervention or control (16 weeks).

• Diet

  Before and after the training intervention or control (16 weeks).

Study Arms (3)

High Intensity Interval Training (HIIT) intervention program

EXPERIMENTAL

The HIIT protocol will involve 3 training sessions per week for 16 weeks (a total of 74 sessions lasting 36 minutes). The high-intensity intervals will follow the Norwegian 4 x 4-minute HIIT model: 4 bouts of 4 minutes of high intensity corresponding to a rating of perceived exertion (RPE) 15 to 18 on the Borg 6 to 20 Scale and an 85-95%HRmax, interspersed with 3-minute active recovery intervals (RPE of 11 to 13 and 54-69%HRmax).

Other: HIIT intervention program

Moderate Intensity Continous Training (MICT) intervention program

EXPERIMENTAL

The MICT protocol will involve 3 training sessions per week for 16 weeks (a total of 74 sessions lasting 44 minutes). The workout will be performed at RPE 11 to 13 (54-69%HRmax) to provide an isoenergetic workload (same energy expenditure) as the HIIT group

Other: MICT intervention program

Control group

NO INTERVENTION

The control group will follow a usual care regime during the intervention and will not participate in supervised exercise. However, the participants randomized to this group will be invited to participate in a similar intervention once the study is completed (waiting list control group).

Interventions

HIIT intervention program OTHER

The HIIT protocol will involve 3 training sessions per week for 18 weeks (a total of 74 sessions lasting 36 minutes). The program will be divided into two phases: phase 1 (adaptation to HIIT training: during the first 4 weeks, the intensity will be progressively increased to ensure the safety and progressive physical conditioning of the patients. The high-intensity intervals will follow the Norwegian 4 x 4-minute HIIT model: 4 bouts of 4 minutes of high intensity corresponding to a rating of perceived exertion (RPE) 15 to 18 on the Borg 6 to 20 Scale33 and an 85-95%HRmax, interspersed with 3-minute active recovery intervals (RPE of 11 to 13 and 54-69%HRmax). This protocol has been widely applied and is safe in general and in clinical populations. Additionally, this protocol includes the training parameters recently proposed in a recent meta-analysis to maximize the training effects of HIIT on cardiorespiratory fitness (primary outcome).

High Intensity Interval Training (HIIT) intervention program

MICT intervention program OTHER

The MICT protocol will involve 3 training sessions per week for 18 weeks (a total of 74 sessions lasting 44 minutes). The workout will be performed at RPE 11 to 13 (54-69%HRmax) to provide an isoenergetic workload (same energy expenditure) as the HIIT group. Each session will include 3 parts: warm-up (5 min), main MICT workout (34 min), and a cool-down (5 min). Warm-up will include mobility, core, and aerobic exercise involving major muscle groups. The main workout (MICT) will include exercises involving major muscle groups using the same materials and rationale as commented on in the HIIT group. The cool-down phase will include aerobic exercise at a lower intensity, stretching, and relaxation exercises (RPE\<11). The highest and average HR and RPE for each session will be registered.

Moderate Intensity Continous Training (MICT) intervention program

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals with a diagnosis of genetic FH.
• \> 18 years old.
• Minimum follow-up of 1 year in the Vascular Risk Clinic of the Virgen de las Nieves University Hospital (HUVN).
• Clinical and treatment stability.
• Non-pathological angio-TAC of coronary arteries in the 5 years prior to the study (for participants \>45 years old).

You may not qualify if:

• Inability to read, understand and sign the informed consent.
• Contraindications to exercise.
• History of clinical CVD (ischemic heart disease, stroke, and/or peripheral arterial disease).

Sponsors & Collaborators

• Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental: lead

Study Sites (1)

Virgen de las Nieves University Hospital

Granada, Granada, 18014, Spain

Location

MeSH Terms

Conditions

Motor Activity; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Behavior

Study Officials

• Jose A Vargas-Hitos, MD, PHD

  Virgen de las Nieves University Hospital, Granada, Spain

  PRINCIPAL INVESTIGATOR

• Alberto Soriano Maldonado, PhD

  Universidad de Almeria

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jose A Vargas-Hitos, MD, PHD

CONTACT

+34625943933; joseantoniovh@hotmail.com

Alberto Soriano-Maldonado, PHD

CONTACT

asoriano@ual.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: José A. Vargas-Hitos, MD, PhD

Model Details: Parallel group randomized and controlled clinical trial

Study Record Dates

• First Submitted: January 27, 2025
• First Posted: February 19, 2025
• Study Start: February 15, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: February 19, 2025

Record last verified: 2025-01

Locations

ES (1)