Geranylgeraniol Supplementation in Patients With Mevalonate Kinase Deficiency

Geranylgeraniol Supplementation in Patients With Mevalonate Kinase Deficiency, MVK Deficiency (hyperIgD Syndrome)

Mevalonate kinase deficiency (HyperIgD syndrome, HIDS) is an inborn error of immunity caused by a block in the mevalonate pathway. The subsequent lack of isoprenoids with antiinflammatory properties might contribute to the autoinflammatory nature of the disease.

A pilot study aims to verify the safety and efficacy of the dietary supplement Geranylgeraniol, aiming at a mitigation of isoprenoids deficiency caused by the above-mentioned block in the MVK pathway.

Study Overview

• Status: Recruiting
• Conditions: Mevalonate Kinase Deficiency
• Intervention / Treatment: Dietary supplement: geranylgeraniol

Detailed Description

Mevalonate kinase (MVK) deficiency, a rare autosomal recessive disease, significantly impacts metabolism and immunity, leading to mevalonic aciduria in severe cases and hyper-IgD syndrome (HIDS) in partial deficiency. These conditions arise due to disruptions in the mevalonate pathway, which is an essential metabolic pathway responsible for the synthesis of non-sterol isoprenoids and other molecules. The resulting metabolic blockade triggers autoinflammatory responses, primarily due to deficient isoprenoid intermediates such as geranylgeranyl pyrophosphate (GGPP).

This study evaluates the safety and efficacy of dietary geranylgeraniol (GG) supplementation in patients with genetically confirmed mevalonate kinase deficiency.

The pilot study consists of a month of a pre-supplementation period to monitor the level of inflammation and clinical status in patients with MVK deficiency(HIDS).

This period is followed by 3 months of supplementation of 150mg of GeranylGraniol (GG Pure (Extendlife Natural Products) containing GG gold®30 Annatto Extract, 500 mg capsule (30% geranylgeraniol, 150 mg per capsule).

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anna Šedivá, Prof; Phone Number: +420603166112; Email: anna.sediva@fnmotol.cz
• Study Contact Backup: Name: Eva Aljamal, Mgr; Phone Number: +420601354311; Email: eva.aljamal@fnmotol.cz

Study Locations

• Czechia
  • Prague, Czechia, 15006
    • Recruiting
    • University Hospital, Motol
    • Contact: Anna Šedivá, Prof; Phone Number: +420 603166112; Email: anna.sediva@fnmotol.cz
    • Contact: Eva Aljamal, Mgr; Phone Number: +420 601354311; Email: eva.aljamal@fnmotol.cz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients older than 12 years with genetically confirmed MVK deficiency
• Overall good clinical status apart from the clinical presentation of the MVK deficiency
• Normal liver tests
• Compliance with the study protocol

Exclusion Criteria:

• Children below 12 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: patients with MVK deficiency; patients fulfilling inclusion criteria	Dietary supplement: geranylgeraniol; GG Pure (Extendlife Natural Products) containing GG gold®30 Annatto Extract, 500 mg capsule, use for 3 months, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in inflammatory parameters	Monitoring inflammatory markers before and after intervention - CRP (C reactive protein) and SAA (serum amyloid A) levels will be measured before and after the intervention (time 0 and time 3 months of GG use). These values tend to be elevated in patients with MVK deficiency due to their inflammatory status compared to normal values defined in clinical laboratories (UHMotol CRP < 8 mg/l, SAA < 10 mg/l). The expected outcome would result in a decrease in inflammatory markers.	3 monhts of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the clinical status of patients	Monitoring of general clinical status and defined parameters - general condition, fatigue, fever, skin manifestations, abdominal pain, and headache using a questionnaire. The questionnaire is designed for daily monitoring of the parameters mentioned above. The scale of the questionnaire is from 1 to 10, with 1 being the best, normal condition, and 10 being the worst degree of disability.	3 months

Collaborators and Investigators

• Sponsor: University Hospital, Motol
• Collaborators: Washington University School of Medicine
• Investigators: Principal Investigator: Anna Šedivá, Mgr, University Hospital, Motol

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 1, 2024
• First Submitted That Met QC Criteria: July 9, 2024
• First Posted (Actual): July 12, 2024

Study Record Updates

• Last Update Posted (Actual): July 12, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: mevalonate kinase; immunoglobulin D; isoprenoids; geranylgeraniol
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Immunoproliferative Disorders; Hematologic Diseases; Genetic Diseases, Inborn; Blood Protein Disorders; Hereditary Autoinflammatory Diseases; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Hypergammaglobulinemia; Peroxisomal Disorders; Mevalonate Kinase Deficiency
• Other Study ID Numbers: EK-30/22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: anonymized patient data consisting of clinical and laboratory sets of follow-up parameters are shared with participating researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No