McArdle DiseaseNCT04044508
Modified Ketogenic Diet in Patients With McArdle Disease Part B
A study testing Ketocal 4:1 liquid Nutricia (intervention) in people with McArdle Disease, run by Copenhagen University Hospital, Rigshospitalet at 2 sites in 2 countries.
Trial summary
McArdle disease, glycogen storage disease type V, is a rare metabolic disease. Affected individuals are unable to utilize sugar stored as glycogen in muscle. Investigators hypothesize that a modified ketogenic diet could be a potential treatment option, by providing ketones as alternative fuel substrates for working… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- McArdle Disease
- What is being tested?
- Ketocal 4:1 liquid Nutricia (intervention)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 3 Aug 2019to 1 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Genetically confirmed GSDV
- Patient is willing and able to provide written informed consent prior to participation.
- Patient is ambulatory.
- Women in fertile age must be willing to practice the following medically acceptable methods of birth control
Who cannot join
- Patient has any prior or current medical conditions that, in the judgment of the Investigator, would prevent the patient from safely participating in and/or completing all study requirements.
- Pregnancy or breastfeeding
- Patient does not have the cognitive capacity to understand/comprehend and complete all study assessments
- Patients with porphyria or disorders of fat metabolism (primary carnitine deficiency, carnitine palmitoyltransferase I or II, β-oxidation defects etc.).
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United Kingdom1 site
National Hospital for Neurology and neurosurgery
London
About this study
Official title: Odified Ketogenic Diet in Patients With McArdle Disease Part B - a Placebo-controlled, Cross-over Study
McArdle disease, glycogen storage disease type V, is a rare metabolic disease. Affected individuals are unable to utilize sugar stored as glycogen in muscle. Investigators hypothesize that a modified ketogenic diet could be a potential treatment option, by providing ketones as alternative fuel substrates for working muscle.
This blinded, placebo-controlled, cross-over study will investigate the potential effects of an optimal modified ketogenic diet found in part A (75% fat, 15%protein, 10%carbohydrates) in patients with McArdle disease compared with a healthy balanced placebo diet (>100grams of carbohydrates per day).
Read the detailed description
A blinded randomized, placebo-controlled, cross-over study to investigate the effects of a modified ketogenic diet in patients with McArdle disease.
McArdle disease, glycogen storage disease type V, is a rare metabolic disease caused by mutations in the PYGM gene resulting in absence of the enzyme muscle phosphorylase. Affected individuals are unable to utilize sugar stored as glycogen in muscle, leading to exercise intolerance, exercise-induced muscle pain, contractures and rhabdomyolysis. Currently, there are no satisfactory treatment options for McArdle disease. Ketones are feasible fuel alternatives to muscle glycogen when muscle glycogenolysis is blocked as in McArdle disease. A key element of alleviating symptoms in McArdle disease is to provide alternative fuels for energy metabolism. Ketosis can potentially provide alternative fuel substrates by provision of endogenous ketone bodies (KBs) which are desirable fuels for skeletal muscle and brain. Ketosis can be reached by fasting and can be induced by adhering to a modified ketogenic diet, which entails a high-fat, low-carbohydrate diet, which simulates the metabolic effects of fasting.
The study design is a placebo-controlled, blind, cross over design. The study will be carried out at two sites: CNMC (Copenhagen), NHNN (London). Subjects will be randomized 1:1 to receive either a modified ketogenic diet (75% fat, 15%protein, 10% carbohydrates) or a placebo diet (>100grams of carbohydrates per day) first. Subjects will follow the diet for 4 weeks, followed by 2-4 weeks wash-out, followed by 4 weeks on the opposite diet. During the 10-12 weeks trial period, subjects will visit the trial site in London on five occasions. Effects of the diet will be evaluated by improvement in exercise capacity during submaximal exercise test on a cycle ergometer. Subjective improvements will be evaluated by questionnaires and a dietary diary.
If the diet improves exercise capacity, it will provide a safe and cheap treatment option that may lead to reduced risk of muscle injury and enhance quality of life in patients with McArdle disease.
- Conditions
- McArdle Disease
- Being tested
- Ketocal 4:1 liquid Nutricia (intervention), Fortini multifibre Nutrica (placebo)
- Medical subject headings
- Glycogen Storage Disease Type V
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketocal 4:1 liquid Nutricia (intervention)Dietary supplement
Modified ketogenic diet
Fortini multifibre Nutrica (placebo)Dietary supplement
Placebo diet
| Study group | Role | What they receive |
|---|---|---|
| Interventional diet | Active comparator | A modified ketogenic diet (with the composition found in the pilot study, 75%fat, 15% protein, 10% carbohydrates) Receives: Dietary Supplement: Ketocal 4:1 liquid Nutricia (intervention) |
| Placebo diet | Placebo comparator | A placebo diet (over 100 g of carbohydrates per day) Receives: Dietary Supplement: Fortini multifibre Nutrica (placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mean heart rate
Change in mean heart rate (bpm) during constant load cycling exercise (30 minute submaximal cycle test). Heart rate will be measured every minute during the cycle test at all visits.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Secondary outcomes (15)
Compliance
Daily dietary diary
Measured: up 12 weeks
Change in Indirect calorimetry
Oxidation rates measured via indirect calorimetry during constant load cycling Measured at visit 1-4.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in self-rated daily function scores
Modified SF-36 questionnaire
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in self-rated fatigue
Fatigue Severity Scale score
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in blood ketones
Ketone bodies in the blood (hydroxybutyrate+acetoacetate umol/L).
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in perceived exertion
Borg scale (scale from 6-20). During the constant load cyclinging test, subjects will be asked every minute during.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in ammonia
Blood Ammonia (umol/L). Will be measured 5 times during the cycle test at visit 1-4.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in insulin
Blood Insulin (pmol/l). Will be measured 6 times during the cycle test at visit 1-4.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in Adrenalin
Blood Adrenalin (pg/mL) Will be measured 6 times during the cycle test at visit 1-4.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in glucagon
Blood Glucagon (pmol/L). Will be measured 4 times during the cycle test at visit 1-4.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in maximal oxygen capacity
(VO2max, mL oxgen per minute) after the 30 minutes submaximal exercise test, the workload will be increased in a step vise manner to maximum.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in maximal work load
Work load (watts) after the 30 minutes submaximal exercise test, the workload will be increased in a step vise manner to maximum.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in free fatty acids
Blood Free fatty acids (umol/L). Will be measured 6 times during the cycle test at visit 1-4.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in lactate
Blood Lactate (mM). Will be measured 6 times during the cycle test at visit 1-4.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in glucose
Blood glucose (mM). Will be measured 6 times during the cycle test at visit 1-4.
Measured: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2019
- Study start3 Aug 2019
- Primary completion1 Oct 2022
- Study completion1 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for McArdle DiseaseStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, blind, placebo-controlled, cross over study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- University College, London
- Responsible party
- Principal investigator, Nicoline Løkken, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04044508
- Sponsor's protocol ID
- H-18013022-B
- Status last verified
- Feb 2023
- First submitted
- 12 Dec 2018
- Last updated
- 13 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lokken N, Nielsen MR, Stemmerik MG, Ellerton C, Revsbech KL, Macrae M, Slipsager A, Krett B, Beha GH, Emanuelsson F, van Hall G, Quinlivan R, Vissing J. Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease? Results from a randomized, single-blind, placebo-controlled, cross-over study. Clin Nutr. 2023 Nov;42(11):2124-2137. doi: 10.1016/j.clnu.2023.09.006. Epub 2023 Sep 20.
PubMed 37769369
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Odified Ketogenic Diet in Patients With McArdle Disease Part B - a Placebo-controlled, Cross-over Study
- ClinicalTrials.gov ID
- NCT04044508
- Acronym / sponsor ID
- H-18013022-B
- Conditions
- McArdle Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- University College, London
- Study start
- 3 Aug 2019 (actual)
- Primary completion
- 1 Oct 2022 (actual)
- Study completion
- 1 Dec 2022 (actual)
- First posted
- 5 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
McArdle disease, glycogen storage disease type V, is a rare metabolic disease. Affected individuals are unable to utilize sugar stored as glycogen in muscle. Investigators hypothesize that a modified ketogenic diet could be a potential treatment option, by providing ketones as alternative fuel substrates for working muscle.
This blinded, placebo-controlled, cross-over study will investigate the potential effects of an optimal modified ketogenic diet found in part A (75% fat, 15%protein, 10%carbohydrates) in patients with McArdle disease compared with a healthy balanced placebo diet (>100grams of carbohydrates per day).
Detailed description
A blinded randomized, placebo-controlled, cross-over study to investigate the effects of a modified ketogenic diet in patients with McArdle disease.
McArdle disease, glycogen storage disease type V, is a rare metabolic disease caused by mutations in the PYGM gene resulting in absence of the enzyme muscle phosphorylase. Affected individuals are unable to utilize sugar stored as glycogen in muscle, leading to exercise intolerance, exercise-induced muscle pain, contractures and rhabdomyolysis. Currently, there are no satisfactory treatment options for McArdle disease. Ketones are feasible fuel alternatives to muscle glycogen when muscle glycogenolysis is blocked as in McArdle disease. A key element of alleviating symptoms in McArdle disease is to provide alternative fuels for energy metabolism. Ketosis can potentially provide alternative fuel substrates by provision of endogenous ketone bodies (KBs) which are desirable fuels for skeletal muscle and brain. Ketosis can be reached by fasting and can be induced by adhering to a modified ketogenic diet, which entails a high-fat, low-carbohydrate diet, which simulates the metabolic effects of fasting.
The study design is a placebo-controlled, blind, cross over design. The study will be carried out at two sites: CNMC (Copenhagen), NHNN (London). Subjects will be randomized 1:1 to receive either a modified ketogenic diet (75% fat, 15%protein, 10% carbohydrates) or a placebo diet (>100grams of carbohydrates per day) first. Subjects will follow the diet for 4 weeks, followed by 2-4 weeks wash-out, followed by 4 weeks on the opposite diet. During the 10-12 weeks trial period, subjects will visit the trial site in London on five occasions. Effects of the diet will be evaluated by improvement in exercise capacity during submaximal exercise test on a cycle ergometer. Subjective improvements will be evaluated by questionnaires and a dietary diary.
If the diet improves exercise capacity, it will provide a safe and cheap treatment option that may lead to reduced risk of muscle injury and enhance quality of life in patients with McArdle disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomized, blind, placebo-controlled, cross over study
| Arm | Type | Receives |
|---|---|---|
| Interventional diet | Active comparator | Dietary Supplement: Ketocal 4:1 liquid Nutricia (intervention)A modified ketogenic diet (with the composition found in the pilot study, 75%fat, 15% protein, 10% carbohydrates) |
| Placebo diet | Placebo comparator | Dietary Supplement: Fortini multifibre Nutrica (placebo)A placebo diet (over 100 g of carbohydrates per day) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Genetically confirmed GSDV
- Patient is willing and able to provide written informed consent prior to participation.
- Patient is ambulatory.
- Women in fertile age must be willing to practice the following medically acceptable methods of birth control
Key exclusion criteria (4 listed)
- Patient has any prior or current medical conditions that, in the judgment of the Investigator, would prevent the patient from safely participating in and/or completing all study requirements.
- Pregnancy or breastfeeding
- Patient does not have the cognitive capacity to understand/comprehend and complete all study assessments
- Patients with porphyria or disorders of fat metabolism (primary carnitine deficiency, carnitine palmitoyltransferase I or II, β-oxidation defects etc.).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketocal 4:1 liquid Nutricia (intervention)Modified ketogenic diet | Dietary supplement | Interventional diet |
| Fortini multifibre Nutrica (placebo)Placebo diet | Dietary supplement | Placebo diet |
Primary outcome
Change in mean heart rate
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in mean heart rate (bpm) during constant load cycling exercise (30 minute submaximal cycle test). Heart rate will be measured every minute during the cycle test at all visits.
15 secondary outcomes
Compliance
Time frame: up 12 weeks
Change in Indirect calorimetry
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in self-rated daily function scores
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in self-rated fatigue
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in blood ketones
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in perceived exertion
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in ammonia
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in insulin
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in Adrenalin
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in glucagon
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in maximal oxygen capacity
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in maximal work load
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in free fatty acids
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in lactate
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Change in glucose
Time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2023.
- Derived from this study: PubMed 37769369Lokken N, Nielsen MR, Stemmerik MG, Ellerton C, Revsbech KL, Macrae M, Slipsager A, Krett B, Beha GH, Emanuelsson F, van Hall G, Quinlivan R, Vissing J. Can a modified ketogenic diet be a nutritional strategy for patients with McArdle disease? Results from a randomized, single-blind, placebo-controlled, cross-over study. Clin Nutr. 2023 Nov;42(11):2124-2137. doi: 10.1016/j.clnu.2023.09.006. Epub 2023 Sep 20.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketocal 4:1 liquid Nutricia (intervention) in people with McArdle Disease, run by Copenhagen University Hospital, Rigshospitalet at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in mean heart rate (time frame: At Visit 1 (baseline), Visit 2 (4 weeks), Visit 3 (8 weeks), and Visit 4 (12 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04044508, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2023.